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Phosphoproteomics Identified an NS5A Phosphorylation Site Involved in Hepatitis C Virus Replication

Chong, Weng Man; Hsu, Shih-Chin; Kao, Wei-Ting; Lo, Chieh-Wen; Lee, Kuan-Ying; Shao, Jheng-Syuan; Chen, Yi-Hung; Chang, Justin; Chen, Steve S-L; Yu, Ming-Jiun
The non-structural protein 5A (NS5A) is a hepatitis C virus (HCV) protein indispensable for the viral life cycle. Many prior papers have pinpointed several serine residues in the low complexity sequence I region of NS5A responsible for NS5A phosphorylation; however, the functions of specific phosphorylation sites remained obscure. Using phosphoproteomics, we identified three phosphorylation sites (serines 222, 235, and 238) in the NS5A low complexity sequence I region. Reporter virus and replicon assays using phosphorylation-ablated alanine mutants of these sites showed that Ser-235 dominated over Ser-222 and Ser-238 in HCV replication. Immunoblotting using an Ser-235 phosphorylation-specific antibody showed a time-dependent increase in Ser-235 phosphorylation that correlated with the viral replication activity. Ser-235 phosphorylated NS5A co-localized with double-stranded RNA, consistent with its role in HCV replication. Mechanistically, Ser-235 phosphorylation probably promotes the replication complex formation via increasing NS5A interaction with the human homologue of the 33-kDa vesicle-associated membrane protein-associated protein. Casein kinase Iα (CKIα) directly phosphorylated Ser-235 in vitro. Inhibition of CKIα reduced Ser-235 phosphorylation and the HCV RNA levels in the infected cells. We concluded that NS5A Ser-235 phosphorylated by CKIα probably promotes HCV replication via increasing NS5A interaction with the 33-kDa vesicle-associated membrane protein-associated protein.
PMCID:4759171
PMID: 26702051
ISSN: 1083-351x
CID: 5392362

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

Klionsky, Daniel J.; Abdelmohsen, Kotb; Abe, Akihisa; Abedin, Md Joynal; Abeliovich, Hagai; Arozena, Abraham Acevedo; Adachi, Hiroaki; Adams, Christopher M.; Adams, Peter D.; Adeli, Khosrow; Adhihetty, Peter J.; Adler, Sharon G.; Agam, Galila; Agarwal, Rajesh; Aghi, Manish K.; Agnello, Maria; Agostinis, Patrizia; Aguilar, Patricia V.; Aguirre-Ghiso, Julio; Airoldi, Edoardo M.; Ait-Si-Ali, Slimane; Akematsu, Takahiko; Akporiaye, Emmanuel T.; Al-Rubeai, Mohamed; Albaiceta, Guillermo M.; Albanese, Chris; Albani, Diego; Albert, Matthew L.; Aldudo, Jesus; Algül, Hana; Alirezaei, Mehrdad; Alloza, Iraide; Almasan, Alexandru; Almonte-Beceril, Maylin; Alnemri, Emad S.; Alonso, Covadonga; Altan-Bonnet, Nihal; Altieri, Dario C.; Alvarez, Silvia; Alvarez-Erviti, Lydia; Alves, Sandro; Amadoro, Giuseppina; Amano, Atsuo; Amantini, Consuelo; Ambrosio, Santiago; Amelio, Ivano; Amer, Amal O.; Amessou, Mohamed; Amon, Angelika; An, Zhenyi; Anania, Frank A.; Andersen, Stig U.; Andley, Usha P.; Andreadi, Catherine K.; Andrieu-Abadie, Nathalie; Anel, Alberto; Ann, David K.; Anoopkumar-Dukie, Shailendra; Antonioli, Manuela; Aoki, Hiroshi; Apostolova, Nadezda; Aquila, Saveria; Aquilano, Katia; Araki, Koichi; Arama, Eli; Aranda, Agustin; Araya, Jun; Arcaro, Alexandre; Arias, Esperanza; Arimoto, Hirokazu; Ariosa, Aileen R.; Armstrong, Jane L.; Arnould, Thierry; Arsov, Ivica; Asanuma, Katsuhiko; Askanas, Valerie; Asselin, Eric; Atarashi, Ryuichiro; Atherton, Sally S.; Atkin, Julie D.; Attardi, Laura D.; Auberger, Patrick; Auburger, Georg; Aurelian, Laure; Autelli, Riccardo; Avagliano, Laura; Avantaggiati, Maria Laura; Avrahami, Limor; Azad, Neelam; Awale, Suresh; Bachetti, Tiziana; Backer, Jonathan M.; Bae, Dong Hun; Bae, Jae Sung; Bae, Ok Nam; Bae, Soo Han; Baehrecke, Eric H.; Baek, Seung Hoon; Baghdiguian, Stephen; Bagniewska-Zadworna, Agnieszka; Bai, Hua; Bai, Jie; Bai, Xue Yuan; Bailly, Yannick; Balaji, Kithiganahalli Narayanaswamy; Balduini, Walter; Ballabio, Andrea; Balzan, Rena; Banerjee, Rajkumar; Bánhegyi, Gábor; Bao, Haijun; Barbeau, Benoit; Barrachina, Maria D.; Barreiro, Esther; Bartel, Bonnie; Bartolomé, Alberto; Bassham, Diane C.; Bassi, Maria Teresa; Bast, Robert C.; Basu, Alakananda; Batista, Maria Teresa; Batoko, Henri; Battino, Maurizio; Bauckman, Kyle; Baumgarner, Bradley L.; Bayer, K. Ulrich; Beale, Rupert; Beaulieu, Jean François; Beck, George R.; Becker, Christoph; Beckham, J. 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Mark; Coppens, Isabelle; Corasaniti, Maria Tiziana; Corazzari, Marco; Corbalan, Ramon; Corcelle-Termeau, Elisabeth; Cordero, Mario D.; Corral-Ramos, Cristina; Corti, Olga; Cossarizza, Andrea; Costelli, Paola; Costes, Safia; Cotman, Susan L.; Coto-Montes, Ana; Cottet, Sandra; Couve, Eduardo; Covey, Lori R.; Cowart, L. Ashley; Cox, Jeffery S.; Coxon, Fraser P.; Coyne, Carolyn B.; Cragg, Mark S.; Craven, Rolf J.; Crepaldi, Tiziana; Crespo, Jose L.; Criollo, Alfredo; Crippa, Valeria; Cruz, Maria Teresa; Cuervo, Ana Maria; Cuezva, Jose M.; Cui, Taixing; Cutillas, Pedro R.; Czaja, Mark J.; Czyzyk-Krzeska, Maria F.; Dagda, Ruben K.; Dahmen, Uta; Dai, Chunsun; Dai, Wenjie; Dai, Yun; Dalby, Kevin N.; Valle, Luisa Dalla; Dalmasso, Guillaume; D'amelio, Marcello; Damme, Markus; Darfeuille-Michaud, Arlette; Dargemont, Catherine; Darley-Usmar, Victor M.; Dasarathy, Srinivasan; Dasgupta, Biplab; Dash, Srikanta; Dass, Crispin R.; Davey, Hazel Marie; Davids, Lester M.; Dávila, David; Davis, Roger J.; Dawson, Ted M.; Dawson, Valina L.; Daza, Paula; de Belleroche, Jackie; de Figueiredo, Paul; de Figueiredo, Regina Celia Bressan Queiroz; de la Fuente, José; De Martino, Luisa; De Matteis, Antonella; De Meyer, Guido R.Y.; De Milito, Angelo; De Santi, Mauro; de Souza, Wanderley; De Tata, Vincenzo; De Zio, Daniela; Debnath, Jayanta; Dechant, Reinhard; Decuypere, Jean Paul; Deegan, Shane; Dehay, Benjamin; Del Bello, Barbara; Del Re, Dominic P.; Delage-Mourroux, Régis; Delbridge, Lea M.D.; Deldicque, Louise; Delorme-Axford, Elizabeth; Deng, Yizhen; Dengjel, Joern; Denizot, Melanie; Dent, Paul; Der, Channing J.; Deretic, Vojo; Derrien, Benoît; Deutsch, Eric; Devarenne, Timothy P.; Devenish, Rodney J.; Di Bartolomeo, Sabrina; Di Daniele, Nicola; Di Domenico, Fabio; Di Nardo, Alessia; Di Paola, Simone; Di Pietro, Antonio; Di Renzo, Livia; Di Antonio, Aaron; Diaz-Araya, Guillermo; Diaz-Laviada, Ines; Diaz-Meco, Maria T.; Diaz-Nido, Javier; Dickey, Chad A.; Dickson, Robert C.; Diederich, Marc; Digard, Paul; Dikic, Ivan; Dinesh-Kumar, Savithrama P.; Ding, Chan; Ding, Wen Xing; Ding, Zufeng; Dini, Luciana; Distler, Jorg H.W.; Diwan, Abhinav; Djavaheri-Mergny, Mojgan; Dmytruk, Kostyantyn; Dobson, Renwick C.J.; Doetsch, Volker; Dokladny, Karol; Dokudovskaya, Svetlana; Donadelli, Massimo; Dong, X. Charlie; Dong, Xiaonan; Dong, Zheng; Donohue, Terrence M.; Donohue-Jr, Terrence M.; Doran, Kelly S.; D'orazi, Gabriella; Dorn, Gerald W.; Dosenko, Victor; Dridi, Sami; Drucker, Liat; Du, Jie; Du, Li Lin; Du, Lihuan; du Toit, André; Dua, Priyamvada; Duan, Lei; Duann, Pu; Dubey, Vikash Kumar; Duchen, Michael R.; Duchosal, Michel A.; Duez, Helene; Dugail, Isabelle; Dumit, Verónica I.; Duncan, Mara C.; Dunlop, Elaine A.; Dunn, William A.; Dupont, Nicolas; Dupuis, Luc; Durán, Raul V.; Durcan, Thomas M.; Duvezin-Caubet, Stéphane; Duvvuri, Umamaheswar; Eapen, Vinay; Ebrahimi-Fakhari, Darius; Echard, Arnaud; Eckhart, Leopold; Edelstein, Charles L.; Edinger, Aimee L.; Eichinger, Ludwig; Eisenberg, Tobias; Eisenberg-Lerner, Avital; Eissa, N. 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Robin; Higaki, Katsumi; Hilfiker, Sabine; Hill, Bradford G.; Hill, Joseph A.; Hill, William D.; Hino, Keisuke; Hofius, Daniel; Hofman, Paul; Hoglinger, Günter U.; Hohfeld, Jorg; Holz, Marina K.; Hong, Yonggeun; Hood, David A.; Hoozemans, Jeroen J.M.; Hoppe, Thorsten; Hsu, Chin; Hsu, Chin Yuan; Hsu, Li Chung; Hu, Dong; Hu, Guochang; Hu, Hong Ming; Hu, Hongbo; Hu, Ming Chang; Hu, Yu Chen; Hu, Zhuo Wei; Hua, Fang; Hua, Ya; Huang, Canhua; Huang, Huey Lan; Huang, Kuo How; Huang, Kuo Yang; Huang, Shile; Huang, Shiqian; Huang, Wei Pang; Huang, Yi Ran; Huang, Yong; Huang, Yunfei; Huber, Tobias B.; Huebbe, Patricia; Huh, Won Ki; Hulmi, Juha J.; Hur, Gang Min; Hurley, James H.; Husak, Zvenyslava; Hussain, Sabah N.A.; Hussain, Salik; Hwang, Jung Jin; Hwang, Seungmin; Hwang, Thomas I.S.; Ichihara, Atsuhiro; Imai, Yuzuru; Imbriano, Carol; Inomata, Megumi; Into, Takeshi; Iovane, Valentina; Iovanna, Juan L.; Iozzo, Renato V.; Ip, Nancy Y.; Irazoqui, Javier E.; Iribarren, Pablo; Isaka, Yoshitaka; Isakovic, Aleksandra J.; Ischiropoulos, Harry; Isenberg, Jeffrey S.; Ishaq, Mohammad; Ishida, Hiroyuki; Ishii, Isao; Ishmael, Jane E.; Isidoro, Ciro; Isobe, Ken Ichi; Isono, Erika; Issazadeh-Navikas, Shohreh; Itahana, Koji; Itakura, Eisuke; Ivanov, Andrei I.; Iyer, Anand Krishnan V.; Izquierdo, José M.; Izumi, Yotaro; Izzo, Valentina; Jäättelä, Marja; Jaber, Nadia; Jackson, Daniel John; Jackson, William T.; Jacob, Tony George; Jacques, Thomas S.; Jagannath, Chinnaswamy; Jain, Ashish; Jana, Nihar Ranjan; Jang, Byoung Kuk; Jani, Alkesh; Janji, Bassam; Jannig, Paulo Roberto; Jansson, Patric J.; Jean, Steve; Jendrach, Marina; Jeon, Ju Hong; Jessen, Niels; Jeung, Eui Bae; Jia, Kailiang; Jia, Lijun; Jiang, Hong; Jiang, Hongchi; Jiang, Liwen; Jiang, Teng; Jiang, Xiaoyan; Jiang, Xuejun; Jiang, Ying; Jiang, Yongjun; Jiménez, Alberto; Jin, Cheng; Jin, Hongchuan; Jin, Lei; Jin, Meiyan; Jin, Shengkan; Jinwal, Umesh Kumar; Jo, Eun Kyeong; Johansen, Terje; Johnson, Daniel E.; Johnson, Gail V.W.; Johnson, James D.; Jonasch, Eric; Jones, Chris; Joosten, Leo A.B.; Jordan, Joaquin; Joseph, Anna Maria; Joseph, Bertrand; Joubert, Annie M.; Ju, Dianwen; Ju, Jingfang; Juan, Hsueh Fen; Juenemann, Katrin; Juhász, Gábor; Jung, Hye Seung; Jung, Jae U.; Jung, Yong Keun; Jungbluth, Heinz; Justice, Matthew J.; Jutten, Barry; Kaakoush, Nadeem O.; Kaarniranta, Kai; Kaasik, Allen; Kabuta, Tomohiro; Kaeffer, Bertrand; Kågedal, Katarina; Kahana, Alon; Kajimura, Shingo; Kakhlon, Or; Kalia, Manjula; Kalvakolanu, Dhan V.; Kamada, Yoshiaki; Kambas, Konstantinos; Kaminskyy, Vitaliy O.; Kampinga, Harm H.; Kandouz, Mustapha; Kang, Chanhee; Kang, Rui; Kang, Tae Cheon; Kanki, Tomotake; Kanneganti, Thirumala Devi; Kanno, Haruo; Kanthasamy, Anumantha G.; Kantorow, Marc; Kaparakis-Liaskos, Maria; Kapuy, Orsolya; Karantza, Vassiliki; Karim, Md Razaul; Karmakar, Parimal; Kaser, Arthur; Kaushik, Susmita; Kawula, Thomas; Kaynar, A. Murat; Ke, Po Yuan; Ke, Zun Ji; Kehrl, John H.; Keller, Kate E.; Kemper, Jongsook Kim; Kenworthy, Anne K.; Kepp, Oliver; Kern, Andreas; Kesari, Santosh; Kessel, David; Ketteler, Robin; Kettelhut, Isis do Carmo; Khambu, Bilon; Khan, Muzamil Majid; Khandelwal, Vinoth K.M.; Khare, Sangeeta; Kiang, Juliann G.; Kiger, Amy A.; Kihara, Akio; Kim, Arianna L.; Kim, Cheol Hyeon; Kim, Deok Ryong; Kim, Do Hyung; Kim, Eung Kweon; Kim, Hye Young; Kim, Hyung Ryong; Kim, Jae Sung; Kim, Jeong Hun; Kim, Jin Cheon; Kim, Jin Hyoung; Kim, Kwang Woon; Kim, Michael D.; Kim, Moon Moo; Kim, Peter K.; Kim, Seong Who; Kim, Soo Youl; Kim, Yong Sun; Kim, Yonghyun; Kimchi, Adi; Kimmelman, Alec C.; Kimura, Tomonori; King, Jason S.; Kirkegaard, Karla; Kirkin, Vladimir; Kirshenbaum, Lorrie A.; Kishi, Shuji; Kitajima, Yasuo; Kitamoto, Katsuhiko; Kitaoka, Yasushi; Kitazato, Kaio; Kley, Rudolf A.; Klimecki, Walter T.; Klinkenberg, Michael; Klucken, Jochen; Knævelsrud, Helene; Knecht, Erwin; Knuppertz, Laura; Ko, Jiunn Liang; Kobayashi, Satoru; Koch, Jan C.; Koechlin-Ramonatxo, Christelle; Koenig, Ulrich; Koh, Young Ho; Kohler, Katja; Kohlwein, Sepp D.; Koike, Masato; Komatsu, Masaaki; Kominami, Eiki; Kong, Dexin; Kong, Hee Jeong; Konstantakou, Eumorphia G.; Kopp, Benjamin T.; Korcsmaros, Tamas; Korhonen, Laura; Korolchuk, Viktor I.; Koshkina, Nadya V.; Kou, Yanjun; Koukourakis, Michael I.; Koumenis, Constantinos; Kovács, Attila L.; Kovács, Tibor; Kovacs, Werner J.; Koya, Daisuke; Kraft, Claudine; Krainc, Dimitri; Kramer, Helmut; Kravic-Stevovic, Tamara; Krek, Wilhelm; Kretz-Remy, Carole; Krick, Roswitha; Krishnamurthy, Malathi; Kriston-Vizi, Janos; Kroemer, Guido; Kruer, Michael C.; Kruger, Rejko; Ktistakis, Nicholas T.; Kuchitsu, Kazuyuki; Kuhn, Christian; Kumar, Addanki Pratap; Kumar, Anuj; Kumar, Ashok; Kumar, Deepak; Kumar, Dhiraj; Kumar, Rakesh; Kumar, Sharad; Kundu, Mondira; Kung, Hsing Jien; Kuno, Atsushi; Kuo, Sheng Han; Kuret, Jeff; Kurz, Tino; Kwok, Terry; Kwon, Taeg Kyu; Kwon, Yong Tae; Kyrmizi, Irene; La Spada, Albert R.; Lafont, Frank; Lahm, Tim; Lakkaraju, Aparna; Lam, Truong; Lamark, Trond; Lancel, Steve; Landowski, Terry H.; Lane, Darius J.R.; Lane, Jon D.; Lanzi, Cinzia; Lapaquette, Pierre; Lapierre, Louis R.; Laporte, Jocelyn; Laukkarinen, Johanna; Laurie, Gordon W.; Lavandero, Sergio; Lavie, Lena; Lavoie, Matthew J.; Law, Betty Yuen Kwan; Law, Helen Ka Wai; Law, Kelsey B.; Layfield, Robert; Lazo, Pedro A.; Le Cam, Laurent; Le Roch, Karine G.; Le Stunff, Hervé; Leardkamolkarn, Vijittra; Lecuit, Marc; Lee, Byung Hoon; Lee, Che Hsin; Lee, Erinna F.; Lee, Gyun Min; Lee, He Jin; Lee, Hsinyu; Lee, Jae Keun; Lee, Jongdae; Lee, Ju Hyun; Lee, Jun Hee; Lee, Michael; Lee, Myung Shik; Lee, Patty J.; Lee, Sam W.; Lee, Seung Jae; Lee, Shiow Ju; Lee, Stella Y.; Lee, Sug Hyung; Lee, Sung Sik; Lee, Sung Joon; Lee, Sunhee; Lee, Ying Ray; Lee, Yong J.; Lee, Young H.; Leeuwenburgh, Christiaan; Lefort, Sylvain; Legouis, Renaud; Lei, Jinzhi; Lei, Qun Ying; Leib, David A.; Leibowitz, Gil; Lekli, Istvan; Lemaire, Stéphane D.; Lemasters, John J.; Lemberg, Marius K.; Lemoine, Antoinette; Leng, Shuilong; Lenz, Guido; Lenzi, Paola; Lerman, Lilach O.; Barbato, Daniele Lettieri; Leu, Julia I.Ju; Leung, Hing Y.; Levine, Beth; Lewis, Patrick A.; Lezoualch, Frank; Li, Chi; Li, Faqiang; Li, Feng Jun; Li, Jun; Li, Ke; Li, Lian; Li, Min; Li, Qiang; Li, Rui; Li, Sheng; Li, Wei; Li, Xiaotao; Li, Yumin; Lian, Jiqin; Liang, Chengyu; Liang, Qiangrong; Liao, Yulin; Liberal, Joana; Liberski, Pawel P.; Lie, Pearl; Lieberman, Andrew P.; Lim, Hyunjung Jade; Lim, Kah Leong; Lim, Kyu; Lima, Raquel T.; Lin, Chang Shen; Lin, Chiou Feng; Lin, Fang; Lin, Fangming; Lin, Fu Cheng; Lin, Kui; Lin, Kwang Huei; Lin, Pei Hui; Lin, Tianwei; Lin, Wan Wan; Lin, Yee Shin; Lin, Yong; Linden, Rafael; Lindholm, Dan; Lindqvist, Lisa M.; Lingor, Paul; Linkermann, Andreas; Liotta, Lance A.; Lipinski, Marta M.; Lira, Vitor A.; Lisanti, Michael P.; Liton, Paloma B.; Liu, Bo; Liu, Chong; Liu, Chun Feng; Liu, Fei; Liu, Hung Jen; Liu, Jianxun; Liu, Jing Jing; Liu, Jing Lan; Liu, Ke; Liu, Leyuan; Liu, Liang; Liu, Quentin; Liu, Rong Yu; Liu, Shiming; Liu, Shuwen; Liu, Wei; Liu, Xian De; Liu, Xiangguo; Liu, Xiao Hong; Liu, Xinfeng; Liu, Xu; Liu, Xueqin; Liu, Yang; Liu, Yule; Liu, Zexian; Liu, Zhe; Liuzzi, Juan P.; Lizard, Gérard; Ljujic, Mila; Lodhi, Irfan J.; Logue, Susan E.; Lokeshwar, Bal L.; Long, Yun Chau; Lonial, Sagar; Loos, Benjamin; López-Otin, Carlos; López-Vicario, Cristina; Lorente, Mar; Lorenzi, Philip L.; Lõrincz, Péter; Los, Marek; Lotze, Michael T.; Lovat, Penny E.; Lu, Binfeng; Lu, Bo; Lu, Jiahong; Lu, Qing; Lu, She Min; Lu, Shuyan; Lu, Yingying; Luciano, Frédéric; Luckhart, Shirley; Lucocq, John Milton; Ludovico, Paula; Lugea, Aurelia; Lukacs, Nicholas W.; Lum, Julian J.; Lund, Anders H.; Luo, Honglin; Luo, Jia; Luo, Shouqing; Luparello, Claudio; Lyons, Timothy; Ma, Jianjie; Ma, Yi; Ma, Yong; Ma, Zhenyi; Machado, Juliano; Machado-Santelli, Glaucia M.; Macian, Fernando; MacIntosh, Gustavo C.; MacKeigan, Jeffrey P.; Macleod, Kay F.; MacMicking, John D.; MacMillan-Crow, Lee Ann; Madeo, Frank; Madesh, Muniswamy; Madrigal-Matute, Julio; Maeda, Akiko; Maeda, Tatsuya; Maegawa, Gustavo; Maellaro, Emilia; Maes, Hannelore; Magariños, Marta; Maiese, Kenneth; Maiti, Tapas K.; Maiuri, Luigi; Maiuri, Maria Chiara; Maki, Carl G.; Malli, Roland; Malorni, Walter; Maloyan, Alina; Mami-Chouaib, Fathia; Man, Na; Mancias, Joseph D.; Mandelkow, Eva Maria; Mandell, Michael A.; Manfredi, Angelo A.; Manié, Serge N.; Manzoni, Claudia; Mao, Kai; Mao, Zixu; Mao, Zong Wan; Marambaud, Philippe; Marconi, Anna Maria; Marelja, Zvonimir; Marfe, Gabriella; Margeta, Marta; Margittai, Eva; Mari, Muriel; Mariani, Francesca V.; Marin, Concepcio; Marinelli, Sara; Mariño, Guillermo; Markovic, Ivanka; Marquez, Rebecca; Martelli, Alberto M.; Martens, Sascha; Martin, Katie R.; Martin, Seamus J.; Martin, Shaun; Martin-Acebes, Miguel A.; Martin-Sanz, Paloma; Martinand-Mari, Camille; Martinet, Wim; Martinez, Jennifer; Martinez-Lopez, Nuria; Martinez-Outschoorn, Ubaldo; Martinez-Velázquez, Moisés; Martinez-Vicente, Marta; Martins, Waleska Kerllen; Mashima, Hirosato; Mastrianni, James A.; Matarese, Giuseppe; Matarrese, Paola; Mateo, Roberto; Matoba, Satoaki; Matsumoto, Naomichi; Matsushita, Takehiko; Matsuura, Akira; Matsuzawa, Takeshi; Mattson, Mark P.; Matus, Soledad; Maugeri, Norma; Mauvezin, Caroline; Mayer, Andreas; Maysinger, Dusica; Mazzolini, Guillermo D.; McBrayer, Mary Kate; McCall, Kimberly; McCormick, Craig; McInerney, Gerald M.; McIver, Skye C.; McKenna, Sharon; McMahon, John J.; McNeish, Iain A.; Mechta-Grigoriou, Fatima; Medema, Jan Paul; Medina, Diego L.; Megyeri, Klara; Mehrpour, Maryam; Mehta, Jawahar L.; Mei, Yide; Meier, Ute Christiane; Meijer, Alfred J.; Meléndez, Alicia; Melino, Gerry; Melino, Sonia; de Melo, Edesio Jose Tenorio; Mena, Maria A.; Meneghini, Marc D.; Menendez, Javier A.; Menezes, Regina; Meng, Liesu; Meng, Ling Hua; Meng, Songshu; Menghini, Rossella; Menko, A. Sue; Menna-Barreto, Rubem F.S.; Menon, Manoj B.; Meraz-Rios, Marco A.; Merla, Giuseppe; Merlini, Luciano; Merlot, Angelica M.; Meryk, Andreas; Meschini, Stefania; Meyer, Joel N.; Mi, Man Tian; Miao, Chao Yu; Micale, Lucia; Michaeli, Simon; Michiels, Carine; Migliaccio, Anna Rita; Mihailidou, Anastasia Susie; Mijaljica, Dalibor; Mikoshiba, Katsuhiko; Milan, Enrico; Miller-Fleming, Leonor; Mills, Gordon B.; Mills, Ian G.; Minakaki, Georgia; Minassian, Berge A.; Ming, Xiu Fen; Minibayeva, Farida; Minina, Elena A.; Mintern, Justine D.; Minucci, Saverio; Miranda-Vizuete, Antonio; Mitchell, Claire H.; Miyamoto, Shigeki; Miyazawa, Keisuke; Mizushima, Noboru; Mnich, Katarzyna; Mograbi, Baharia; Mohseni, Simin; Moita, Luis Ferreira; Molinari, Marco; Molinari, Maurizio; Møller, Andreas Buch; Mollereau, Bertrand; Mollinedo, Faustino; Mongillo, Marco; Monick, Martha M.; Montagnaro, Serena; Montell, Craig; Moore, Darren J.; Moore, Michael N.; Mora-Rodriguez, Rodrigo; Moreira, Paula I.; Morel, Etienne; Morelli, Maria Beatrice; Moreno, Sandra; Morgan, Michael J.; Moris, Arnaud; Moriyasu, Yuji; Morrison, Janna L.; Morrison, Lynda A.; Morselli, Eugenia; Moscat, Jorge; Moseley, Pope L.; Mostowy, Serge; Motori, Elisa; Mottet, Denis; Mottram, Jeremy C.; Moussa, Charbel E.H.; Mpakou, Vassiliki E.; Mukhtar, Hasan; Levy, Jean M.Mulcahy; Muller, Sylviane; Muñoz-Moreno, Raquel; Muñoz-Pinedo, Cristina; Münz, Christian; Murphy, Maureen E.; Murray, James T.; Murthy, Aditya; Mysorekar, Indira U.; Nabi, Ivan R.; Nabissi, Massimo; Nader, Gustavo A.; Nagahara, Yukitoshi; Nagai, Yoshitaka; Nagata, Kazuhiro; Nagelkerke, Anika; Nagy, Péter; Naidu, Samisubbu R.; Nair, Sreejayan; Nakano, Hiroyasu; Nakatogawa, Hitoshi; Nanjundan, Meera; Napolitano, Gennaro; Naqvi, Naweed I.; Nardacci, Roberta; Narendra, Derek P.; Narita, Masashi; Nascimbeni, Anna Chiara; Natarajan, Ramesh; Navegantes, Luiz C.; Nawrocki, Steffan T.; Nazarko, Taras Y.; Nazarko, Volodymyr Y.; Neill, Thomas; Neri, Luca M.; Netea, Mihai G.; Netea-Maier, Romana T.; Neves, Bruno M.; Ney, Paul A.; Nezis, Ioannis P.; Nguyen, Hang T.T.; Nguyen, Huu Phuc; Nicot, Anne Sophie; Nilsen, Hilde; Nilsson, Per; Nishimura, Mikio; Nishino, Ichizo; Niso-Santano, Mireia; Niu, Hua; Nixon, Ralph A.; Njar, Vincent C.O.; Noda, Takeshi; Noegel, Angelika A.; Nolte, Elsie Magdalena; Norberg, Erik; Norga, Koenraad K.; Noureini, Sakineh Kazemi; Notomi, Shoji; Notterpek, Lucia; Nowikovsky, Karin; Nukina, Nobuyuki; Nürnberger, Thorsten; O'donnell, Valerie B.; O'donovan, Tracey; O'dwyer, Peter J.; Oehme, Ina; Oeste, Clara L.; Ogawa, Michinaga; Ogretmen, Besim; Ogura, Yuji; Oh, Young J.; Ohmuraya, Masaki; Ohshima, Takayuki; Ojha, Rani; Okamoto, Koji; Okazaki, Toshiro; Oliver, F. Javier; Ollinger, Karin; Olsson, Stefan; Orban, Daniel P.; Ordonez, Paulina; Orhon, Idil; Orosz, Laszlo; O'rourke, Eyleen J.; Orozco, Helena; Ortega, Angel L.; Ortona, Elena; Osellame, Laura D.; Oshima, Junko; Oshima, Shigeru; Osiewacz, Heinz D.; Otomo, Takanobu; Otsu, Kinya; Ou, Jing Hsiung James; Outeiro, Tiago F.; Ouyang, Dong Yun; Ouyang, Hongjiao; Overholtzer, Michael; Ozbun, Michelle A.; Ozdinler, P. Hande; Ozpolat, Bulent; Pacelli, Consiglia; Paganetti, Paolo; Page, Guyléne; Pages, Gilles; Pagnini, Ugo; Pajak, Beata; Pak, Stephen C.; Pakos-Zebrucka, Karolina; Pakpour, Nazzy; Palková, Zdena; Palladino, Francesca; Pallauf, Kathrin; Pallet, Nicolas; Palmieri, Marta; Paludan, Søren R.; Palumbo, Camilla; Palumbo, Silvia; Pampliega, Olatz; Pan, Hongming; Pan, Wei; Panaretakis, Theocharis; Pandey, Aseem; Pantazopoulou, Areti; Papackova, Zuzana; Papademetrio, Daniela L.; Papassideri, Issidora; Papini, Alessio; Parajuli, Nirmala; Pardo, Julian; Parekh, Vrajesh V.; Parenti, Giancarlo; Park, Jong In; Park, Junsoo; Park, Ohkmae K.; Parker, Roy; Parlato, Rosanna; Parys, Jan B.; Parzych, Katherine R.; Pasquet, Jean Max; Pasquier, Benoit; Pasumarthi, Kishore B.S.; Patschan, Daniel; Pattingre, Sophie; Pattison, Scott; Pause, Arnim; Pavenstädt, Hermann; Pavone, Flaminia; Pedrozo, Zully; Peña, Fernando J.; Peñalva, Miguel A.; Pende, Mario; Peng, Jianxin; Penna, Fabio; Penninger, Josef M.; Pensalfini, Anna; Pepe, Salvatore; Pereira, Gustavo J.S.; Pereira, Paulo C.; de la Cruz, Verónica Pérez; Pérez-Pérez, Maria Esther; Pérez-Rodriguez, Diego; Pérez-Sala, Dolores; Perier, Celine; Perl, Andras; Perlmutter, David H.; Perrotta, Ida; Pervaiz, Shazib; Pesonen, Maija; Pessin, Jeffrey E.; Peters, Godefridus J.; Petersen, Morten; Petrache, Irina; Petrof, Basil J.; Petrovski, Goran; Phang, James M.; Piacentini, Mauro; Pierdominici, Marina; Pierre, Philippe; Pierrefite-Carle, Valérie; Pietrocola, Federico; Pimentel-Muiños, Felipe X.; Pinar, Mario; Pineda, Benjamin; Pinkas-Kramarski, Ronit; Pinti, Marcello; Pinton, Paolo; Piperdi, Bilal; Piret, James M.; Platanias, Leonidas C.; Platta, Harald W.; Plowey, Edward D.; Poggeler, Stefanie; Poirot, Marc; Polcic, Peter; Poletti, Angelo; Poon, Audrey H.; Popelka, Hana; Popova, Blagovesta; Poprawa, Izabela; Poulose, Shibu M.; Poulton, Joanna; Powers, Scott K.; Powers, Ted; Pozuelo-Rubio, Mercedes; Prak, Krisna; Prange, Reinhild; Prescott, Mark; Priault, Muriel; Prince, Sharon; Proia, Richard L.; Proikas-Cezanne, Tassula; Prokisch, Holger; Promponas, Vasilis J.; Przyklenk, Karin; Puertollano, Rosa; Pugazhenthi, Subbiah; Puglielli, Luigi; Pujol, Aurora; Puyal, Julien; Pyeon, Dohun; Qi, Xin; Qian, Wen Bin; Qin, Zheng Hong; Qiu, Yu; Qu, Ziwei; Quadrilatero, Joe; Quinn, Frederick; Raben, Nina; Rabinowich, Hannah; Radogna, Flavia; Ragusa, Michael J.; Rahmani, Mohamed; Raina, Komal; Ramanadham, Sasanka; Ramesh, Rajagopal; Rami, Abdelhaq; Randall-Demllo, Sarron; Randow, Felix; Rao, Hai; Rao, V. Ashutosh; Rasmussen, Blake B.; Rasse, Tobias M.; Ratovitski, Edward A.; Rautou, Pierre Emmanuel; Ray, Swapan K.; Razani, Babak; Reed, Bruce H.; Reggiori, Fulvio; Rehm, Markus; Reichert, Andreas S.; Rein, Theo; Reiner, David J.; Reits, Eric; Ren, Jun; Ren, Xingcong; Renna, Maurizio; Reusch, Jane E.B.; Revuelta, Jose L.; Reyes, Leticia; Rezaie, Alireza R.; Richards, Robert I.; Richardson, Des R.; Richetta, Clémence; Riehle, Michael A.; Rihn, Bertrand H.; Rikihisa, Yasuko; Riley, Brigit E.; Rimbach, Gerald; Rippo, Maria Rita; Ritis, Konstantinos; Rizzi, Federica; Rizzo, Elizete; Roach, Peter J.; Robbins, Jeffrey; Roberge, Michel; Roca, Gabriela; Roccheri, Maria Carmela; Rocha, Sonia; Rodrigues, Cecilia M.P.; Rodriguez, Clara I.; de Cordoba, Santiago Rodriguez; Rodriguez-Muela, Natalia; Roelofs, Jeroen; Rogov, Vladimir V.; Rohn, Troy T.; Rohrer, Bärbel; Romanelli, Davide; Romani, Luigina; Romano, Patricia Silvia; Roncero, M. Isabel G.; Rosa, Jose Luis; Rosello, Alicia; Rosen, Kirill V.; Rosenstiel, Philip; Rost-Roszkowska, Magdalena; Roth, Kevin A.; Roué, Gael; Rouis, Mustapha; Rouschop, Kasper M.; Ruan, Daniel T.; Ruano, Diego; Rubinsztein, David C.; Rucker, Edmund B.; Rudich, Assaf; Rudolf, Emil; Rudolf, Ruediger; Ruegg, Markus A.; Ruiz-Roldan, Carmen; Ruparelia, Avnika Ashok; Rusmini, Paola; Russ, David W.; Russo, Gian Luigi; Russo, Giuseppe; Russo, Rossella; Rusten, Tor Erik; Ryabovol, Victoria; Ryan, Kevin M.; Ryter, Stefan W.; Sabatini, David M.; Sacher, Michael; Sachse, Carsten; Sack, Michael N.; Sadoshima, Junichi; Saftig, Paul; Sagi-Eisenberg, Ronit; Sahni, Sumit; Saikumar, Pothana; Saito, Tsunenori; Saitoh, Tatsuya; Sakakura, Koichi; Sakoh-Nakatogawa, Machiko; Sakuraba, Yasuhito; Salazar-Roa, Maria; Salomoni, Paolo; Saluja, Ashok K.; Salvaterra, Paul M.; Salvioli, Rosa; Samali, Afshin; Sanchez, Anthony M.J.; Sánchez-Alcázar, José A.; Sanchez-Prieto, Ricardo; Sandri, Marco; Sanjuan, Miguel A.; Santaguida, Stefano; Santambrogio, Laura; Santoni, Giorgio; Dos Santos, Claudia Nunes; Saran, Shweta; Sardiello, Marco; Sargent, Graeme; Sarkar, Pallabi; Sarkar, Sovan; Sarrias, Maria Rosa; Sarwal, Minnie M.; Sasakawa, Chihiro; Sasaki, Motoko; Sass, Miklos; Sato, Ken; Sato, Miyuki; Satriano, Joseph; Savaraj, Niramol; Saveljeva, Svetlana; Schaefer, Liliana; Schaible, Ulrich E.; Scharl, Michael; Schatzl, Hermann M.; Schekman, Randy; Scheper, Wiep; Schiavi, Alfonso; Schipper, Hyman M.; Schmeisser, Hana; Schmidt, Jens; Schmitz, Ingo; Schneider, Bianca E.; Schneider, E. Marion; Schneider, Jaime L.; Schon, Eric A.; Schonenberger, Miriam J.; Schonthal, Axel H.; Schorderet, Daniel F.; Schroder, Bernd; Schuck, Sebastian; Schulze, Ryan J.; Schwarten, Melanie; Schwarz, Thomas L.; Sciarretta, Sebastiano; Scotto, Kathleen; Scovassi, A. Ivana; Screaton, Robert A.; Screen, Mark; Seca, Hugo; Sedej, Simon; Segatori, Laura; Segev, Nava; Seglen, Per O.; Segui-Simarro, Jose M.; Segura-Aguilar, Juan; Seiliez, Iban; Seki, Ekihiro; Sell, Christian; Semenkovich, Clay F.; Semenza, Gregg L.; Sen, Utpal; Serra, Andreas L.; Serrano-Puebla, Ana; Sesaki, Hiromi; Setoguchi, Takao; Settembre, Carmine; Shacka, John J.; Shajahan-Haq, Ayesha N.; Shapiro, Irving M.; Sharma, Shweta; She, Hua; Shen, C. 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SCOPUS:85054826264
ISSN: 1554-8627
CID: 5487622

Emerging roles of interferon-stimulated genes in the innate immune response to hepatitis C virus infection

Wong, Mun-Teng; Chen, Steve S-L
Infection with hepatitis C virus (HCV), a major viral cause of chronic liver disease, frequently progresses to steatosis and cirrhosis, which can lead to hepatocellular carcinoma. HCV infection strongly induces host responses, such as the activation of the unfolded protein response, autophagy and the innate immune response. Upon HCV infection, the host induces the interferon (IFN)-mediated frontline defense to limit virus replication. Conversely, HCV employs diverse strategies to escape host innate immune surveillance. Type I IFN elicits its antiviral actions by inducing a wide array of IFN-stimulated genes (ISGs). Nevertheless, the mechanisms by which these ISGs participate in IFN-mediated anti-HCV actions remain largely unknown. In this review, we first outline the signaling pathways known to be involved in the production of type I IFN and ISGs and the tactics that HCV uses to subvert innate immunity. Then, we summarize the effector mechanisms of scaffold ISGs known to modulate IFN function in HCV replication. We also highlight the potential functions of emerging ISGs, which were identified from genome-wide siRNA screens, in HCV replication. Finally, we discuss the functions of several cellular determinants critical for regulating host immunity in HCV replication. This review will provide a basis for understanding the complexity and functionality of the pleiotropic IFN system in HCV infection. Elucidation of the specificity and the mode of action of these emerging ISGs will also help to identify novel cellular targets against which effective HCV therapeutics can be developed.
PMCID:4712384
PMID: 25544499
ISSN: 2042-0226
CID: 5392352

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) [Guideline]

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Chan, Matthew Tv; Chandra, Dhyan; Chandra, Pallavi; Chang, Chih-Peng; Chang, Raymond Chuen-Chung; Chang, Ta Yuan; Chatham, John C; Chatterjee, Saurabh; Chauhan, Santosh; Che, Yongsheng; Cheetham, Michael E; Cheluvappa, Rajkumar; Chen, Chun-Jung; Chen, Gang; Chen, Guang-Chao; Chen, Guoqiang; Chen, Hongzhuan; Chen, Jeff W; Chen, Jian-Kang; Chen, Min; Chen, Mingzhou; Chen, Peiwen; Chen, Qi; Chen, Quan; Chen, Shang-Der; Chen, Si; Chen, Steve S-L; Chen, Wei; Chen, Wei-Jung; Chen, Wen Qiang; Chen, Wenli; Chen, Xiangmei; Chen, Yau-Hung; Chen, Ye-Guang; Chen, Yin; Chen, Yingyu; Chen, Yongshun; Chen, Yu-Jen; Chen, Yue-Qin; Chen, Yujie; Chen, Zhen; Chen, Zhong; Cheng, Alan; Cheng, Christopher Hk; Cheng, Hua; Cheong, Heesun; Cherry, Sara; Chesney, Jason; Cheung, Chun Hei Antonio; Chevet, Eric; Chi, Hsiang Cheng; Chi, Sung-Gil; Chiacchiera, Fulvio; Chiang, Hui-Ling; Chiarelli, Roberto; Chiariello, Mario; Chieppa, Marcello; Chin, Lih-Shen; Chiong, Mario; Chiu, Gigi Nc; Cho, Dong-Hyung; Cho, Ssang-Goo; Cho, William C; Cho, Yong-Yeon; Cho, Young-Seok; Choi, Augustine Mk; Choi, Eui-Ju; Choi, Eun-Kyoung; Choi, Jayoung; Choi, Mary E; Choi, Seung-Il; Chou, Tsui-Fen; Chouaib, Salem; Choubey, Divaker; Choubey, Vinay; Chow, Kuan-Chih; Chowdhury, Kamal; Chu, Charleen T; Chuang, Tsung-Hsien; Chun, Taehoon; Chung, Hyewon; Chung, Taijoon; Chung, Yuen-Li; Chwae, Yong-Joon; Cianfanelli, Valentina; Ciarcia, Roberto; Ciechomska, Iwona A; Ciriolo, Maria Rosa; Cirone, Mara; Claerhout, Sofie; Clague, Michael J; Claria, Joan; Clarke, Peter Gh; Clarke, Robert; Clementi, Emilio; Cleyrat, Cedric; Cnop, Miriam; Coccia, Eliana M; Cocco, Tiziana; Codogno, Patrice; Coers, Jorn; Cohen, Ezra Ew; Colecchia, David; Coletto, Luisa; Coll, Nuria S; Colucci-Guyon, Emma; Comincini, Sergio; Condello, Maria; Cook, Katherine L; Coombs, Graham H; Cooper, Cynthia D; Cooper, J Mark; Coppens, Isabelle; Corasaniti, Maria Tiziana; Corazzari, Marco; Corbalan, Ramon; Corcelle-Termeau, Elisabeth; Cordero, Mario D; Corral-Ramos, Cristina; Corti, Olga; Cossarizza, Andrea; Costelli, Paola; Costes, Safia; Cotman, Susan L; Coto-Montes, Ana; Cottet, Sandra; Couve, Eduardo; Covey, Lori R; Cowart, L Ashley; Cox, Jeffery S; Coxon, Fraser P; Coyne, Carolyn B; Cragg, Mark S; Craven, Rolf J; Crepaldi, Tiziana; Crespo, Jose L; Criollo, Alfredo; Crippa, Valeria; Cruz, Maria Teresa; Cuervo, Ana Maria; Cuezva, Jose M; Cui, Taixing; Cutillas, Pedro R; Czaja, Mark J; Czyzyk-Krzeska, Maria F; Dagda, Ruben K; Dahmen, Uta; Dai, Chunsun; Dai, Wenjie; Dai, Yun; Dalby, Kevin N; Dalla Valle, Luisa; Dalmasso, Guillaume; D'Amelio, Marcello; Damme, Markus; Darfeuille-Michaud, Arlette; Dargemont, Catherine; Darley-Usmar, Victor M; Dasarathy, Srinivasan; Dasgupta, Biplab; Dash, Srikanta; Dass, Crispin R; Davey, Hazel Marie; Davids, Lester M; Davila, David; Davis, Roger J; Dawson, Ted M; Dawson, Valina L; Daza, Paula; de Belleroche, Jackie; de Figueiredo, Paul; de Figueiredo, Regina Celia Bressan Queiroz; de la Fuente, Jose; De Martino, Luisa; De Matteis, Antonella; De Meyer, Guido Ry; De Milito, Angelo; De Santi, Mauro; de Souza, Wanderley; De Tata, Vincenzo; De Zio, Daniela; Debnath, Jayanta; Dechant, Reinhard; Decuypere, Jean-Paul; Deegan, Shane; Dehay, Benjamin; Del Bello, Barbara; Del Re, Dominic P; Delage-Mourroux, Regis; Delbridge, Lea Md; Deldicque, Louise; Delorme-Axford, Elizabeth; Deng, Yizhen; Dengjel, Joern; Denizot, Melanie; Dent, Paul; Der, Channing J; Deretic, Vojo; Derrien, Benoit; Deutsch, Eric; Devarenne, Timothy P; Devenish, Rodney J; Di Bartolomeo, Sabrina; Di Daniele, Nicola; Di Domenico, Fabio; Di Nardo, Alessia; Di Paola, Simone; Di Pietro, Antonio; Di Renzo, Livia; DiAntonio, Aaron; Diaz-Araya, Guillermo; Diaz-Laviada, Ines; Diaz-Meco, Maria T; Diaz-Nido, Javier; Dickey, Chad A; Dickson, Robert C; Diederich, Marc; Digard, Paul; Dikic, Ivan; Dinesh-Kumar, Savithrama P; Ding, Chan; Ding, Wen-Xing; Ding, Zufeng; Dini, Luciana; Distler, Jorg Hw; Diwan, Abhinav; Djavaheri-Mergny, Mojgan; Dmytruk, Kostyantyn; Dobson, Renwick Cj; Doetsch, Volker; Dokladny, Karol; Dokudovskaya, Svetlana; Donadelli, Massimo; Dong, X Charlie; Dong, Xiaonan; Dong, Zheng; Donohue, Terrence M Jr; Doran, Kelly S; D'Orazi, Gabriella; Dorn, Gerald W 2nd; Dosenko, Victor; Dridi, Sami; Drucker, Liat; Du, Jie; Du, Li-Lin; Du, Lihuan; du Toit, Andre; Dua, Priyamvada; Duan, Lei; Duann, Pu; Dubey, Vikash Kumar; Duchen, Michael R; Duchosal, Michel A; Duez, Helene; Dugail, Isabelle; Dumit, Veronica I; Duncan, Mara C; Dunlop, Elaine A; Dunn, William A Jr; Dupont, Nicolas; Dupuis, Luc; Duran, Raul V; Durcan, Thomas M; Duvezin-Caubet, Stephane; Duvvuri, Umamaheswar; Eapen, Vinay; Ebrahimi-Fakhari, Darius; Echard, Arnaud; Eckhart, Leopold; Edelstein, Charles L; Edinger, Aimee L; Eichinger, Ludwig; Eisenberg, Tobias; Eisenberg-Lerner, Avital; Eissa, N Tony; El-Deiry, Wafik S; El-Khoury, Victoria; Elazar, Zvulun; Eldar-Finkelman, Hagit; Elliott, Chris Jh; Emanuele, Enzo; Emmenegger, Urban; Engedal, Nikolai; Engelbrecht, Anna-Mart; Engelender, Simone; Enserink, Jorrit M; Erdmann, Ralf; Erenpreisa, Jekaterina; Eri, Rajaraman; Eriksen, Jason L; Erman, Andreja; Escalante, Ricardo; Eskelinen, Eeva-Liisa; Espert, Lucile; Esteban-Martinez, Lorena; Evans, Thomas J; Fabri, Mario; Fabrias, Gemma; Fabrizi, Cinzia; Facchiano, Antonio; Faergeman, Nils J; Faggioni, Alberto; Fairlie, W Douglas; Fan, Chunhai; Fan, Daping; Fan, Jie; Fang, Shengyun; Fanto, Manolis; Fanzani, Alessandro; Farkas, Thomas; Faure, Mathias; Favier, Francois B; Fearnhead, Howard; Federici, Massimo; Fei, Erkang; Felizardo, Tania C; Feng, Hua; Feng, Yibin; Feng, Yuchen; Ferguson, Thomas A; Fernandez, Alvaro F; Fernandez-Barrena, Maite G; Fernandez-Checa, Jose C; Fernandez-Lopez, Arsenio; Fernandez-Zapico, Martin E; Feron, Olivier; Ferraro, Elisabetta; Ferreira-Halder, Carmen Verissima; Fesus, Laszlo; Feuer, Ralph; Fiesel, Fabienne C; Filippi-Chiela, Eduardo C; Filomeni, Giuseppe; Fimia, Gian Maria; Fingert, John H; Finkbeiner, Steven; Finkel, Toren; Fiorito, Filomena; Fisher, Paul B; Flajolet, Marc; Flamigni, Flavio; Florey, Oliver; Florio, Salvatore; Floto, R Andres; Folini, Marco; Follo, Carlo; Fon, Edward A; Fornai, Francesco; Fortunato, Franco; Fraldi, Alessandro; Franco, Rodrigo; Francois, Arnaud; Francois, Aurelie; Frankel, Lisa B; Fraser, Iain Dc; Frey, Norbert; Freyssenet, Damien G; Frezza, Christian; Friedman, Scott L; Frigo, Daniel E; Fu, Dongxu; Fuentes, Jose M; Fueyo, Juan; Fujitani, Yoshio; Fujiwara, Yuuki; Fujiya, Mikihiro; Fukuda, Mitsunori; Fulda, Simone; Fusco, Carmela; Gabryel, Bozena; Gaestel, Matthias; Gailly, Philippe; Gajewska, Malgorzata; Galadari, Sehamuddin; Galili, Gad; Galindo, Inmaculada; Galindo, Maria F; Galliciotti, Giovanna; Galluzzi, Lorenzo; Galluzzi, Luca; Galy, Vincent; Gammoh, Noor; Gandy, Sam; Ganesan, Anand K; Ganesan, Swamynathan; Ganley, Ian G; Gannage, Monique; Gao, Fen-Biao; Gao, Feng; Gao, Jian-Xin; Garcia Nannig, Lorena; Garcia Vescovi, Eleonora; Garcia-Macia, Marina; Garcia-Ruiz, Carmen; Garg, Abhishek D; Garg, Pramod Kumar; Gargini, Ricardo; Gassen, Nils Christian; Gatica, Damian; Gatti, Evelina; Gavard, Julie; Gavathiotis, Evripidis; Ge, Liang; Ge, Pengfei; Ge, Shengfang; Gean, Po-Wu; Gelmetti, Vania; Genazzani, Armando A; Geng, Jiefei; Genschik, Pascal; Gerner, Lisa; Gestwicki, Jason E; Gewirtz, David A; Ghavami, Saeid; Ghigo, Eric; Ghosh, Debabrata; Giammarioli, Anna Maria; Giampieri, Francesca; Giampietri, Claudia; Giatromanolaki, Alexandra; Gibbings, Derrick J; Gibellini, Lara; Gibson, Spencer B; Ginet, Vanessa; Giordano, Antonio; Giorgini, Flaviano; Giovannetti, Elisa; Girardin, Stephen E; Gispert, Suzana; Giuliano, Sandy; Gladson, Candece L; Glavic, Alvaro; Gleave, Martin; Godefroy, Nelly; Gogal, Robert M Jr; Gokulan, Kuppan; Goldman, Gustavo H; Goletti, Delia; Goligorsky, Michael S; Gomes, Aldrin V; Gomes, Ligia C; Gomez, Hernando; Gomez-Manzano, Candelaria; Gomez-Sanchez, Ruben; Goncalves, Dawit Ap; Goncu, Ebru; Gong, Qingqiu; Gongora, Celine; Gonzalez, Carlos B; Gonzalez-Alegre, Pedro; Gonzalez-Cabo, Pilar; Gonzalez-Polo, Rosa Ana; Goping, Ing Swie; Gorbea, Carlos; Gorbunov, Nikolai V; Goring, Daphne R; Gorman, Adrienne M; Gorski, Sharon M; Goruppi, Sandro; Goto-Yamada, Shino; Gotor, Cecilia; Gottlieb, Roberta A; Gozes, Illana; Gozuacik, Devrim; Graba, Yacine; Graef, Martin; Granato, Giovanna E; Grant, Gary Dean; Grant, Steven; Gravina, Giovanni Luca; Green, Douglas R; Greenhough, Alexander; Greenwood, Michael T; Grimaldi, Benedetto; Gros, Frederic; Grose, Charles; Groulx, Jean-Francois; Gruber, Florian; Grumati, Paolo; Grune, Tilman; Guan, Jun-Lin; Guan, Kun-Liang; Guerra, Barbara; Guillen, Carlos; Gulshan, Kailash; Gunst, Jan; Guo, Chuanyong; Guo, Lei; Guo, Ming; Guo, Wenjie; Guo, Xu-Guang; Gust, Andrea A; Gustafsson, Asa B; Gutierrez, Elaine; Gutierrez, Maximiliano G; Gwak, Ho-Shin; Haas, Albert; Haber, James E; Hadano, Shinji; Hagedorn, Monica; Hahn, David R; Halayko, Andrew J; Hamacher-Brady, Anne; Hamada, Kozo; Hamai, Ahmed; Hamann, Andrea; Hamasaki, Maho; Hamer, Isabelle; Hamid, Qutayba; Hammond, Ester M; Han, Feng; Han, Weidong; Handa, James T; Hanover, John A; Hansen, Malene; Harada, Masaru; Harhaji-Trajkovic, Ljubica; Harper, J Wade; Harrath, Abdel Halim; Harris, Adrian L; Harris, James; Hasler, Udo; Hasselblatt, Peter; Hasui, Kazuhisa; Hawley, Robert G; Hawley, Teresa S; He, Congcong; He, Cynthia Y; He, Fengtian; He, Gu; He, Rong-Rong; He, Xian-Hui; He, You-Wen; He, Yu-Ying; Heath, Joan K; Hebert, Marie-Josee; Heinzen, Robert A; Helgason, Gudmundur Vignir; Hensel, Michael; Henske, Elizabeth P; Her, Chengtao; Herman, Paul K; Hernandez, Agustin; Hernandez, Carlos; Hernandez-Tiedra, Sonia; Hetz, Claudio; Hiesinger, P Robin; Higaki, Katsumi; Hilfiker, Sabine; Hill, Bradford G; Hill, Joseph A; Hill, William D; Hino, Keisuke; Hofius, Daniel; Hofman, Paul; Hoglinger, Gunter U; Hohfeld, Jorg; Holz, Marina K; Hong, Yonggeun; Hood, David A; Hoozemans, Jeroen Jm; Hoppe, Thorsten; Hsu, Chin; Hsu, Chin-Yuan; Hsu, Li-Chung; Hu, Dong; Hu, Guochang; Hu, Hong-Ming; Hu, Hongbo; Hu, Ming Chang; Hu, Yu-Chen; Hu, Zhuo-Wei; Hua, Fang; Hua, Ya; Huang, Canhua; Huang, Huey-Lan; Huang, Kuo-How; Huang, Kuo-Yang; Huang, Shile; Huang, Shiqian; Huang, Wei-Pang; Huang, Yi-Ran; Huang, Yong; Huang, Yunfei; Huber, Tobias B; Huebbe, Patricia; Huh, Won-Ki; Hulmi, Juha J; Hur, Gang Min; Hurley, James H; Husak, Zvenyslava; Hussain, Sabah Na; Hussain, Salik; Hwang, Jung Jin; Hwang, Seungmin; Hwang, Thomas Is; Ichihara, Atsuhiro; Imai, Yuzuru; Imbriano, Carol; Inomata, Megumi; Into, Takeshi; Iovane, Valentina; Iovanna, Juan L; Iozzo, Renato V; Ip, Nancy Y; Irazoqui, Javier E; Iribarren, Pablo; Isaka, Yoshitaka; Isakovic, Aleksandra J; Ischiropoulos, Harry; Isenberg, Jeffrey S; Ishaq, Mohammad; Ishida, Hiroyuki; Ishii, Isao; Ishmael, Jane E; Isidoro, Ciro; Isobe, Ken-Ichi; Isono, Erika; Issazadeh-Navikas, Shohreh; Itahana, Koji; Itakura, Eisuke; Ivanov, Andrei I; Iyer, Anand Krishnan V; Izquierdo, Jose M; Izumi, Yotaro; Izzo, Valentina; Jaattela, Marja; Jaber, Nadia; Jackson, Daniel John; Jackson, William T; Jacob, Tony George; Jacques, Thomas S; Jagannath, Chinnaswamy; Jain, Ashish; Jana, Nihar Ranjan; Jang, Byoung Kuk; Jani, Alkesh; Janji, Bassam; Jannig, Paulo Roberto; Jansson, Patric J; Jean, Steve; Jendrach, Marina; Jeon, Ju-Hong; Jessen, Niels; Jeung, Eui-Bae; Jia, Kailiang; Jia, Lijun; Jiang, Hong; Jiang, Hongchi; Jiang, Liwen; Jiang, Teng; Jiang, Xiaoyan; Jiang, Xuejun; Jiang, Xuejun; Jiang, Ying; Jiang, Yongjun; Jimenez, Alberto; Jin, Cheng; Jin, Hongchuan; Jin, Lei; Jin, Meiyan; Jin, Shengkan; Jinwal, Umesh Kumar; Jo, Eun-Kyeong; Johansen, Terje; Johnson, Daniel E; Johnson, Gail Vw; Johnson, James D; Jonasch, Eric; Jones, Chris; Joosten, Leo Ab; Jordan, Joaquin; Joseph, Anna-Maria; Joseph, Bertrand; Joubert, Annie M; Ju, Dianwen; Ju, Jingfang; Juan, Hsueh-Fen; Juenemann, Katrin; Juhasz, Gabor; Jung, Hye Seung; Jung, Jae U; Jung, Yong-Keun; Jungbluth, Heinz; Justice, Matthew J; Jutten, Barry; Kaakoush, Nadeem O; Kaarniranta, Kai; Kaasik, Allen; Kabuta, Tomohiro; Kaeffer, Bertrand; Kagedal, Katarina; Kahana, Alon; Kajimura, Shingo; Kakhlon, Or; Kalia, Manjula; Kalvakolanu, Dhan V; Kamada, Yoshiaki; Kambas, Konstantinos; Kaminskyy, Vitaliy O; Kampinga, Harm H; Kandouz, Mustapha; Kang, Chanhee; Kang, Rui; Kang, Tae-Cheon; Kanki, Tomotake; Kanneganti, Thirumala-Devi; Kanno, Haruo; Kanthasamy, Anumantha G; Kantorow, Marc; Kaparakis-Liaskos, Maria; Kapuy, Orsolya; Karantza, Vassiliki; Karim, Md Razaul; Karmakar, Parimal; Kaser, Arthur; Kaushik, Susmita; Kawula, Thomas; Kaynar, A Murat; Ke, Po-Yuan; Ke, Zun-Ji; Kehrl, John H; Keller, Kate E; Kemper, Jongsook Kim; Kenworthy, Anne K; Kepp, Oliver; Kern, Andreas; Kesari, Santosh; Kessel, David; Ketteler, Robin; Kettelhut, Isis do Carmo; Khambu, Bilon; Khan, Muzamil Majid; Khandelwal, Vinoth Km; Khare, Sangeeta; Kiang, Juliann G; Kiger, Amy A; Kihara, Akio; Kim, Arianna L; Kim, Cheol Hyeon; Kim, Deok Ryong; Kim, Do-Hyung; Kim, Eung Kweon; Kim, Hye Young; Kim, Hyung-Ryong; Kim, Jae-Sung; Kim, Jeong Hun; Kim, Jin Cheon; Kim, Jin Hyoung; Kim, Kwang Woon; Kim, Michael D; Kim, Moon-Moo; Kim, Peter K; Kim, Seong Who; Kim, Soo-Youl; Kim, Yong-Sun; Kim, Yonghyun; Kimchi, Adi; Kimmelman, Alec C; Kimura, Tomonori; King, Jason S; Kirkegaard, Karla; Kirkin, Vladimir; Kirshenbaum, Lorrie A; Kishi, Shuji; Kitajima, Yasuo; Kitamoto, Katsuhiko; Kitaoka, Yasushi; Kitazato, Kaio; Kley, Rudolf A; Klimecki, Walter T; Klinkenberg, Michael; Klucken, Jochen; Knaevelsrud, Helene; Knecht, Erwin; Knuppertz, Laura; Ko, Jiunn-Liang; Kobayashi, Satoru; Koch, Jan C; Koechlin-Ramonatxo, Christelle; Koenig, Ulrich; Koh, Young Ho; Kohler, Katja; Kohlwein, Sepp D; Koike, Masato; Komatsu, Masaaki; Kominami, Eiki; Kong, Dexin; Kong, Hee Jeong; Konstantakou, Eumorphia G; Kopp, Benjamin T; Korcsmaros, Tamas; Korhonen, Laura; Korolchuk, Viktor I; Koshkina, Nadya V; Kou, Yanjun; Koukourakis, Michael I; Koumenis, Constantinos; Kovacs, Attila L; Kovacs, Tibor; Kovacs, Werner J; Koya, Daisuke; Kraft, Claudine; Krainc, Dimitri; Kramer, Helmut; Kravic-Stevovic, Tamara; Krek, Wilhelm; Kretz-Remy, Carole; Krick, Roswitha; Krishnamurthy, Malathi; Kriston-Vizi, Janos; Kroemer, Guido; Kruer, Michael C; Kruger, Rejko; Ktistakis, Nicholas T; Kuchitsu, Kazuyuki; Kuhn, Christian; Kumar, Addanki Pratap; Kumar, Anuj; Kumar, Ashok; Kumar, Deepak; Kumar, Dhiraj; Kumar, Rakesh; Kumar, Sharad; Kundu, Mondira; Kung, Hsing-Jien; Kuno, Atsushi; Kuo, Sheng-Han; Kuret, Jeff; Kurz, Tino; Kwok, Terry; Kwon, Taeg Kyu; Kwon, Yong Tae; Kyrmizi, Irene; La Spada, Albert R; Lafont, Frank; Lahm, Tim; Lakkaraju, Aparna; Lam, Truong; Lamark, Trond; Lancel, Steve; Landowski, Terry H; Lane, Darius Jr; Lane, Jon D; Lanzi, Cinzia; Lapaquette, Pierre; Lapierre, Louis R; Laporte, Jocelyn; Laukkarinen, Johanna; Laurie, Gordon W; Lavandero, Sergio; Lavie, Lena; LaVoie, Matthew J; Law, Betty Yuen Kwan; Law, Helen Ka-Wai; Law, Kelsey B; Layfield, Robert; Lazo, Pedro A; Le Cam, Laurent; Le Roch, Karine G; Le Stunff, Herve; Leardkamolkarn, Vijittra; Lecuit, Marc; Lee, Byung-Hoon; Lee, Che-Hsin; Lee, Erinna F; Lee, Gyun Min; Lee, He-Jin; Lee, Hsinyu; Lee, Jae Keun; Lee, Jongdae; Lee, Ju-Hyun; Lee, Jun Hee; Lee, Michael; Lee, Myung-Shik; Lee, Patty J; Lee, Sam W; Lee, Seung-Jae; Lee, Shiow-Ju; Lee, Stella Y; Lee, Sug Hyung; Lee, Sung Sik; Lee, Sung-Joon; Lee, Sunhee; Lee, Ying-Ray; Lee, Yong J; Lee, Young H; Leeuwenburgh, Christiaan; Lefort, Sylvain; Legouis, Renaud; Lei, Jinzhi; Lei, Qun-Ying; Leib, David A; Leibowitz, Gil; Lekli, Istvan; Lemaire, Stephane D; Lemasters, John J; Lemberg, Marius K; Lemoine, Antoinette; Leng, Shuilong; Lenz, Guido; Lenzi, Paola; Lerman, Lilach O; Lettieri Barbato, Daniele; Leu, Julia I-Ju; Leung, Hing Y; Levine, Beth; Lewis, Patrick A; Lezoualc'h, Frank; Li, Chi; Li, Faqiang; Li, Feng-Jun; Li, Jun; Li, Ke; Li, Lian; Li, Min; Li, Min; Li, Qiang; Li, Rui; Li, Sheng; Li, Wei; Li, Wei; Li, Xiaotao; Li, Yumin; Lian, Jiqin; Liang, Chengyu; Liang, Qiangrong; Liao, Yulin; Liberal, Joana; Liberski, Pawel P; Lie, Pearl; Lieberman, Andrew P; Lim, Hyunjung Jade; Lim, Kah-Leong; Lim, Kyu; Lima, Raquel T; Lin, Chang-Shen; Lin, Chiou-Feng; Lin, Fang; Lin, Fangming; Lin, Fu-Cheng; Lin, Kui; Lin, Kwang-Huei; Lin, Pei-Hui; Lin, Tianwei; Lin, Wan-Wan; Lin, Yee-Shin; Lin, Yong; Linden, Rafael; Lindholm, Dan; Lindqvist, Lisa M; Lingor, Paul; Linkermann, Andreas; Liotta, Lance A; Lipinski, Marta M; Lira, Vitor A; Lisanti, Michael P; Liton, Paloma B; Liu, Bo; Liu, Chong; Liu, Chun-Feng; Liu, Fei; Liu, Hung-Jen; Liu, Jianxun; Liu, Jing-Jing; Liu, Jing-Lan; Liu, Ke; Liu, Leyuan; Liu, Liang; Liu, Quentin; Liu, Rong-Yu; Liu, Shiming; Liu, Shuwen; Liu, Wei; Liu, Xian-De; Liu, Xiangguo; Liu, Xiao-Hong; Liu, Xinfeng; Liu, Xu; Liu, Xueqin; Liu, Yang; Liu, Yule; Liu, Zexian; Liu, Zhe; Liuzzi, Juan P; Lizard, Gerard; Ljujic, Mila; Lodhi, Irfan J; Logue, Susan E; Lokeshwar, Bal L; Long, Yun Chau; Lonial, Sagar; Loos, Benjamin; Lopez-Otin, Carlos; Lopez-Vicario, Cristina; Lorente, Mar; Lorenzi, Philip L; Lorincz, Peter; Los, Marek; Lotze, Michael T; Lovat, Penny E; Lu, Binfeng; Lu, Bo; Lu, Jiahong; Lu, Qing; Lu, She-Min; Lu, Shuyan; Lu, Yingying; Luciano, Frederic; Luckhart, Shirley; Lucocq, John Milton; Ludovico, Paula; Lugea, Aurelia; Lukacs, Nicholas W; Lum, Julian J; Lund, Anders H; Luo, Honglin; Luo, Jia; Luo, Shouqing; Luparello, Claudio; Lyons, Timothy; Ma, Jianjie; Ma, Yi; Ma, Yong; Ma, Zhenyi; Machado, Juliano; Machado-Santelli, Glaucia M; Macian, Fernando; MacIntosh, Gustavo C; MacKeigan, Jeffrey P; Macleod, Kay F; MacMicking, John D; MacMillan-Crow, Lee Ann; Madeo, Frank; Madesh, Muniswamy; Madrigal-Matute, Julio; Maeda, Akiko; Maeda, Tatsuya; Maegawa, Gustavo; Maellaro, Emilia; Maes, Hannelore; Magarinos, Marta; Maiese, Kenneth; Maiti, Tapas K; Maiuri, Luigi; Maiuri, Maria Chiara; Maki, Carl G; Malli, Roland; Malorni, Walter; Maloyan, Alina; Mami-Chouaib, Fathia; Man, Na; Mancias, Joseph D; Mandelkow, Eva-Maria; Mandell, Michael A; Manfredi, Angelo A; Manie, Serge N; Manzoni, Claudia; Mao, Kai; Mao, Zixu; Mao, Zong-Wan; Marambaud, Philippe; Marconi, Anna Maria; Marelja, Zvonimir; Marfe, Gabriella; Margeta, Marta; Margittai, Eva; Mari, Muriel; Mariani, Francesca V; Marin, Concepcio; Marinelli, Sara; Marino, Guillermo; Markovic, Ivanka; Marquez, Rebecca; Martelli, Alberto M; Martens, Sascha; Martin, Katie R; Martin, Seamus J; Martin, Shaun; Martin-Acebes, Miguel A; Martin-Sanz, Paloma; Martinand-Mari, Camille; Martinet, Wim; Martinez, Jennifer; Martinez-Lopez, Nuria; Martinez-Outschoorn, Ubaldo; Martinez-Velazquez, Moises; Martinez-Vicente, Marta; Martins, Waleska Kerllen; Mashima, Hirosato; Mastrianni, James A; Matarese, Giuseppe; Matarrese, Paola; Mateo, Roberto; Matoba, Satoaki; Matsumoto, Naomichi; Matsushita, Takehiko; Matsuura, Akira; Matsuzawa, Takeshi; Mattson, Mark P; Matus, Soledad; Maugeri, Norma; Mauvezin, Caroline; Mayer, Andreas; Maysinger, Dusica; Mazzolini, Guillermo D; McBrayer, Mary Kate; McCall, Kimberly; McCormick, Craig; McInerney, Gerald M; McIver, Skye C; McKenna, Sharon; McMahon, John J; McNeish, Iain A; 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PMCID:4835977
PMID: 26799652
ISSN: 1554-8635
CID: 1922322

Autophagy in hepatitis C virus-host interactions: potential roles and therapeutic targets for liver-associated diseases

Ke, Po-Yuan; Chen, Steve S-L
Autophagy is a lysosome-associated, degradative process that catabolizes cytosolic components to recycle nutrients for further use and maintain cell homeostasis. Hepatitis C virus (HCV) is a major cause of chronic hepatitis, which often leads to end-stage liver-associated diseases and is a significant burden on worldwide public health. Emerging lines of evidence indicate that autophagy plays an important role in promoting the HCV life cycle in host cells. Moreover, the diverse impacts of autophagy on a variety of signaling pathways in HCV-infected cells suggest that the autophagic process is required for balancing HCV-host cell interactions and involved in the pathogenesis of HCV-related liver diseases. However, the detailed molecular mechanism underlying how HCV activates autophagy to benefit viral growth is still enigmatic. Additionally, how the autophagic response contributes to disease progression in HCV-infected cells remains largely unknown. Hence, in this review, we overview the interplay between autophagy and the HCV life cycle and propose possible mechanisms by which autophagy may promote the pathogenesis of HCV-associated chronic liver diseases. Moreover, we outline the related studies on how autophagy interplays with HCV replication and discuss the possible implications of autophagy and viral replication in the progression of HCV-induced liver diseases, e.g., steatosis and hepatocellular carcinoma. Finally, we explore the potential therapeutics that target autophagy to cure HCV infection and its related liver diseases.
PMCID:4024787
PMID: 24914338
ISSN: 2219-2840
CID: 5392342

Active RNA replication of hepatitis C virus downregulates CD81 expression

Ke, Po-Yuan; Chen, Steve S-L
So far how hepatitis C virus (HCV) replication modulates subsequent virus growth and propagation still remains largely unknown. Here we determine the impact of HCV replication status on the consequential virus growth by comparing normal and high levels of HCV RNA expression. We first engineered a full-length, HCV genotype 2a JFH1 genome containing a blasticidin-resistant cassette inserted at amino acid residue of 420 in nonstructural (NS) protein 5A, which allowed selection of human hepatoma Huh7 cells stably-expressing HCV. Short-term establishment of HCV stable cells attained a highly-replicating status, judged by higher expressions of viral RNA and protein as well as higher titer of viral infectivity as opposed to cells harboring the same genome without selection. Interestingly, maintenance of highly-replicating HCV stable cells led to decreased susceptibility to HCV pseudotyped particle (HCVpp) infection and downregulated cell surface level of CD81, a critical HCV entry (co)receptor. The decreased CD81 cell surface expression occurred through reduced total expression and cytoplasmic retention of CD81 within an endoplasmic reticulum -associated compartment. Moreover, productive viral RNA replication in cells harboring a JFH1 subgenomic replicon containing a similar blasticidin resistance gene cassette in NS5A and in cells robustly replicating full-length infectious genome also reduced permissiveness to HCVpp infection through decreasing the surface expression of CD81. The downregulation of CD81 surface level in HCV RNA highly-replicating cells thus interfered with reinfection and led to attenuated viral amplification. These findings together indicate that the HCV RNA replication status plays a crucial determinant in HCV growth by modulating the expression and intracellular localization of CD81.
PMCID:3551917
PMID: 23349980
ISSN: 1932-6203
CID: 5392332

Hepatitis C virus and cellular stress response: implications to molecular pathogenesis of liver diseases

Ke, Po-Yuan; Chen, Steve S-L
Infection with hepatitis C virus (HCV) is a leading risk factor for chronic liver disease progression, including steatosis, cirrhosis, and hepatocellular carcinoma. With approximately 3% of the human population infected worldwide, HCV infection remains a global public health challenge. The efficacy of current therapy is still limited in many patients infected with HCV, thus a greater understanding of pathogenesis in HCV infection is desperately needed. Emerging lines of evidence indicate that HCV triggers a wide range of cellular stress responses, including cell cycle arrest, apoptosis, endoplasmic reticulum (ER) stress/unfolded protein response (UPR), and autophagy. Also, recent studies suggest that these HCV-induced cellular responses may contribute to chronic liver diseases by modulating cell proliferation, altering lipid metabolism, and potentiating oncogenic pathways. However, the molecular mechanism underlying HCV infection in the pathogenesis of chronic liver diseases still remains to be determined. Here, we review the known stress response activation in HCV infection in vitro and in vivo, and also explore the possible relationship of a variety of cellular responses with the pathogenicity of HCV-associated diseases. Comprehensive knowledge of HCV-mediated disease progression shall shed new insights into the discovery of novel therapeutic targets and the development of new intervention strategy.
PMCID:3497051
PMID: 23202463
ISSN: 1999-4915
CID: 5392322

Guidelines for the use and interpretation of assays for monitoring autophagy [Guideline]

Klionsky, Daniel J; Abdalla, Fabio C; Abeliovich, Hagai; Abraham, Robert T; Acevedo-Arozena, Abraham; Adeli, Khosrow; Agholme, Lotta; Agnello, Maria; Agostinis, Patrizia; Aguirre-Ghiso, Julio A; Ahn, Hyung Jun; Ait-Mohamed, Ouardia; Ait-Si-Ali, Slimane; Akematsu, Takahiko; Akira, Shizuo; Al-Younes, Hesham M; Al-Zeer, Munir A; Albert, Matthew L; Albin, Roger L; Alegre-Abarrategui, Javier; Aleo, Maria Francesca; Alirezaei, Mehrdad; Almasan, Alexandru; Almonte-Becerril, Maylin; Amano, Atsuo; Amaravadi, Ravi; Amarnath, Shoba; Amer, Amal O; Andrieu-Abadie, Nathalie; Anantharam, Vellareddy; Ann, David K; Anoopkumar-Dukie, Shailendra; Aoki, Hiroshi; Apostolova, Nadezda; Arancia, Giuseppe; Aris, John P; Asanuma, Katsuhiko; Asare, Nana Y O; Ashida, Hisashi; Askanas, Valerie; Askew, David S; Auberger, Patrick; Baba, Misuzu; Backues, Steven K; Baehrecke, Eric H; Bahr, Ben A; Bai, Xue-Yuan; Bailly, Yannick; Baiocchi, Robert; Baldini, Giulia; Balduini, Walter; Ballabio, Andrea; Bamber, Bruce A; Bampton, Edward T W; Banhegyi, Gabor; Bartholomew, Clinton R; Bassham, Diane C; Bast, Robert C Jr; Batoko, Henri; Bay, Boon-Huat; Beau, Isabelle; Bechet, Daniel M; Begley, Thomas J; Behl, Christian; Behrends, Christian; Bekri, Soumeya; Bellaire, Bryan; Bendall, Linda J; Benetti, Luca; Berliocchi, Laura; Bernardi, Henri; Bernassola, Francesca; Besteiro, Sebastien; Bhatia-Kissova, Ingrid; Bi, Xiaoning; Biard-Piechaczyk, Martine; Blum, Janice S; Boise, Lawrence H; Bonaldo, Paolo; Boone, David L; Bornhauser, Beat C; Bortoluci, Karina R; Bossis, Ioannis; Bost, Frederic; Bourquin, Jean-Pierre; Boya, Patricia; Boyer-Guittaut, Michael; Bozhkov, Peter V; Brady, Nathan R; Brancolini, Claudio; Brech, Andreas; Brenman, Jay E; Brennand, Ana; Bresnick, Emery H; Brest, Patrick; Bridges, Dave; Bristol, Molly L; Brookes, Paul S; Brown, Eric J; Brumell, John H; Brunetti-Pierri, Nicola; Brunk, Ulf T; Bulman, Dennis E; Bultman, Scott J; Bultynck, Geert; Burbulla, Lena F; Bursch, Wilfried; Butchar, Jonathan P; Buzgariu, Wanda; Bydlowski, Sergio P; Cadwell, Ken; Cahova, Monika; Cai, Dongsheng; Cai, Jiyang; Cai, Qian; Calabretta, Bruno; Calvo-Garrido, Javier; Camougrand, Nadine; Campanella, Michelangelo; Campos-Salinas, Jenny; Candi, Eleonora; Cao, Lizhi; Caplan, Allan B; Carding, Simon R; Cardoso, Sandra M; Carew, Jennifer S; Carlin, Cathleen R; Carmignac, Virginie; Carneiro, Leticia A M; Carra, Serena; Caruso, Rosario A; Casari, Giorgio; Casas, Caty; Castino, Roberta; Cebollero, Eduardo; Cecconi, Francesco; Celli, Jean; Chaachouay, Hassan; Chae, Han-Jung; Chai, Chee-Yin; Chan, David C; Chan, Edmond Y; Chang, Raymond Chuen-Chung; Che, Chi-Ming; Chen, Ching-Chow; Chen, Guang-Chao; Chen, Guo-Qiang; Chen, Min; Chen, Quan; Chen, Steve S-L; Chen, WenLi; Chen, Xi; Chen, Xiangmei; Chen, Xiequn; Chen, Ye-Guang; Chen, Yingyu; Chen, Yongqiang; Chen, Yu-Jen; Chen, Zhixiang; Cheng, Alan; Cheng, Christopher H K; Cheng, Yan; Cheong, Heesun; Cheong, Jae-Ho; Cherry, Sara; Chess-Williams, Russ; Cheung, Zelda H; Chevet, Eric; Chiang, Hui-Ling; Chiarelli, Roberto; Chiba, Tomoki; Chin, Lih-Shen; Chiou, Shih-Hwa; Chisari, Francis V; Cho, Chi Hin; Cho, Dong-Hyung; Choi, Augustine M K; Choi, DooSeok; Choi, Kyeong Sook; Choi, Mary E; Chouaib, Salem; Choubey, Divaker; Choubey, Vinay; Chu, Charleen T; Chuang, Tsung-Hsien; Chueh, Sheau-Huei; Chun, Taehoon; Chwae, Yong-Joon; Chye, Mee-Len; Ciarcia, Roberto; Ciriolo, Maria R; Clague, Michael J; Clark, Robert S B; Clarke, Peter G H; Clarke, Robert; Codogno, Patrice; Coller, Hilary A; Colombo, Maria I; Comincini, Sergio; Condello, Maria; Condorelli, Fabrizio; Cookson, Mark R; Coombs, Graham H; Coppens, Isabelle; Corbalan, Ramon; Cossart, Pascale; Costelli, Paola; Costes, Safia; Coto-Montes, Ana; Couve, Eduardo; Coxon, Fraser P; Cregg, James M; Crespo, Jose L; Cronje, Marianne J; Cuervo, Ana Maria; Cullen, Joseph J; Czaja, Mark J; D'Amelio, Marcello; Darfeuille-Michaud, Arlette; Davids, Lester M; Davies, Faith E; De Felici, Massimo; de Groot, John F; de Haan, Cornelis A M; De Martino, Luisa; De Milito, Angelo; De Tata, Vincenzo; Debnath, Jayanta; Degterev, Alexei; Dehay, Benjamin; Delbridge, Lea M D; Demarchi, Francesca; Deng, Yi Zhen; Dengjel, Jorn; Dent, Paul; Denton, Donna; Deretic, Vojo; Desai, Shyamal D; Devenish, Rodney J; Di Gioacchino, Mario; Di Paolo, Gilbert; Di Pietro, Chiara; Diaz-Araya, Guillermo; Diaz-Laviada, Ines; Diaz-Meco, Maria T; Diaz-Nido, Javier; Dikic, Ivan; Dinesh-Kumar, Savithramma P; Ding, Wen-Xing; Distelhorst, Clark W; Diwan, Abhinav; Djavaheri-Mergny, Mojgan; Dokudovskaya, Svetlana; Dong, Zheng; Dorsey, Frank C; Dosenko, Victor; Dowling, James J; Doxsey, Stephen; Dreux, Marlene; Drew, Mark E; Duan, Qiuhong; Duchosal, Michel A; Duff, Karen; Dugail, Isabelle; Durbeej, Madeleine; Duszenko, Michael; Edelstein, Charles L; Edinger, Aimee L; Egea, Gustavo; Eichinger, Ludwig; Eissa, N Tony; Ekmekcioglu, Suhendan; El-Deiry, Wafik S; Elazar, Zvulun; Elgendy, Mohamed; Ellerby, Lisa M; Eng, Kai Er; Engelbrecht, Anna-Mart; Engelender, Simone; Erenpreisa, Jekaterina; Escalante, Ricardo; Esclatine, Audrey; Eskelinen, Eeva-Liisa; Espert, Lucile; Espina, Virginia; Fan, Huizhou; Fan, Jia; Fan, Qi-Wen; Fan, Zhen; Fang, Shengyun; Fang, Yongqi; Fanto, Manolis; Fanzani, Alessandro; Farkas, Thomas; Farre, Jean-Claude; Faure, Mathias; Fechheimer, Marcus; Feng, Carl G; Feng, Jian; Feng, Qili; Feng, Youji; Fesus, Laszlo; Feuer, Ralph; Figueiredo-Pereira, Maria E; Fimia, Gian Maria; Fingar, Diane C; Finkbeiner, Steven; Finkel, Toren; Finley, Kim D; Fiorito, Filomena; Fisher, Edward A; Fisher, Paul B; Flajolet, Marc; Florez-McClure, Maria L; Florio, Salvatore; Fon, Edward A; Fornai, Francesco; Fortunato, Franco; Fotedar, Rati; Fowler, Daniel H; Fox, Howard S; Franco, Rodrigo; Frankel, Lisa B; Fransen, Marc; Fuentes, Jose M; Fueyo, Juan; Fujii, Jun; Fujisaki, Kozo; Fujita, Eriko; Fukuda, Mitsunori; Furukawa, Ruth H; Gaestel, Matthias; Gailly, Philippe; Gajewska, Malgorzata; Galliot, Brigitte; Galy, Vincent; Ganesh, Subramaniam; Ganetzky, Barry; Ganley, Ian G; Gao, Fen-Biao; Gao, George F; Gao, Jinming; Garcia, Lorena; Garcia-Manero, Guillermo; Garcia-Marcos, Mikel; Garmyn, Marjan; Gartel, Andrei L; Gatti, Evelina; Gautel, Mathias; Gawriluk, Thomas R; Gegg, Matthew E; Geng, Jiefei; Germain, Marc; Gestwicki, Jason E; Gewirtz, David A; Ghavami, Saeid; Ghosh, Pradipta; Giammarioli, Anna M; Giatromanolaki, Alexandra N; Gibson, Spencer B; Gilkerson, Robert W; Ginger, Michael L; Ginsberg, Henry N; Golab, Jakub; Goligorsky, Michael S; Golstein, Pierre; Gomez-Manzano, Candelaria; Goncu, Ebru; Gongora, Celine; Gonzalez, Claudio D; Gonzalez, Ramon; Gonzalez-Estevez, Cristina; Gonzalez-Polo, Rosa Ana; Gonzalez-Rey, Elena; Gorbunov, Nikolai V; Gorski, Sharon; Goruppi, Sandro; Gottlieb, Roberta A; Gozuacik, Devrim; Granato, Giovanna Elvira; Grant, Gary D; Green, Kim N; Gregorc, Ales; Gros, Frederic; Grose, Charles; Grunt, Thomas W; Gual, Philippe; Guan, Jun-Lin; Guan, Kun-Liang; Guichard, Sylvie M; Gukovskaya, Anna S; Gukovsky, Ilya; Gunst, Jan; Gustafsson, Asa B; Halayko, Andrew J; Hale, Amber N; Halonen, Sandra K; Hamasaki, Maho; Han, Feng; Han, Ting; Hancock, Michael K; Hansen, Malene; Harada, Hisashi; Harada, Masaru; Hardt, Stefan E; Harper, J Wade; Harris, Adrian L; Harris, James; Harris, Steven D; Hashimoto, Makoto; Haspel, Jeffrey A; Hayashi, Shin-ichiro; Hazelhurst, Lori A; He, Congcong; He, You-Wen; Hebert, Marie-Josee; Heidenreich, Kim A; Helfrich, Miep H; Helgason, Gudmundur V; Henske, Elizabeth P; Herman, Brian; Herman, Paul K; Hetz, Claudio; Hilfiker, Sabine; Hill, Joseph A; Hocking, Lynne J; Hofman, Paul; Hofmann, Thomas G; Hohfeld, Jorg; Holyoake, Tessa L; Hong, Ming-Huang; Hood, David A; Hotamisligil, Gokhan S; Houwerzijl, Ewout J; Hoyer-Hansen, Maria; Hu, Bingren; Hu, Chien-An A; Hu, Hong-Ming; Hua, Ya; Huang, Canhua; Huang, Ju; Huang, Shengbing; Huang, Wei-Pang; Huber, Tobias B; Huh, Won-Ki; Hung, Tai-Ho; Hupp, Ted R; Hur, Gang Min; Hurley, James B; Hussain, Sabah N A; Hussey, Patrick J; Hwang, Jung Jin; Hwang, Seungmin; Ichihara, Atsuhiro; Ilkhanizadeh, Shirin; Inoki, Ken; Into, Takeshi; Iovane, Valentina; Iovanna, Juan L; Ip, Nancy Y; Isaka, Yoshitaka; Ishida, Hiroyuki; Isidoro, Ciro; Isobe, Ken-ichi; Iwasaki, Akiko; Izquierdo, Marta; Izumi, Yotaro; Jaakkola, Panu M; Jaattela, Marja; Jackson, George R; Jackson, William T; Janji, Bassam; Jendrach, Marina; Jeon, Ju-Hong; Jeung, Eui-Bae; Jiang, Hong; Jiang, Hongchi; Jiang, Jean X; Jiang, Ming; Jiang, Qing; Jiang, Xuejun; Jiang, Xuejun; Jimenez, Alberto; Jin, Meiyan; Jin, Shengkan; Joe, Cheol O; Johansen, Terje; Johnson, Daniel E; Johnson, Gail V W; Jones, Nicola L; Joseph, Bertrand; Joseph, Suresh K; Joubert, Annie M; Juhasz, Gabor; Juillerat-Jeanneret, Lucienne; Jung, Chang Hwa; Jung, Yong-Keun; Kaarniranta, Kai; Kaasik, Allen; Kabuta, Tomohiro; Kadowaki, Motoni; Kagedal, Katarina; Kamada, Yoshiaki; Kaminskyy, Vitaliy O; Kampinga, Harm H; Kanamori, Hiromitsu; Kang, Chanhee; Kang, Khong Bee; Kang, Kwang Il; Kang, Rui; Kang, Yoon-A; Kanki, Tomotake; Kanneganti, Thirumala-Devi; Kanno, Haruo; Kanthasamy, Anumantha G; Kanthasamy, Arthi; Karantza, Vassiliki; Kaushal, Gur P; Kaushik, Susmita; Kawazoe, Yoshinori; Ke, Po-Yuan; Kehrl, John H; Kelekar, Ameeta; Kerkhoff, Claus; Kessel, David H; Khalil, Hany; Kiel, Jan A K W; Kiger, Amy A; Kihara, Akio; Kim, Deok Ryong; Kim, Do-Hyung; Kim, Dong-Hou; Kim, Eun-Kyoung; Kim, Hyung-Ryong; Kim, Jae-Sung; Kim, Jeong Hun; Kim, Jin Cheon; Kim, John K; Kim, Peter K; Kim, Seong Who; Kim, Yong-Sun; Kim, Yonghyun; Kimchi, Adi; Kimmelman, Alec C; King, Jason S; Kinsella, Timothy J; Kirkin, Vladimir; Kirshenbaum, Lorrie A; Kitamoto, Katsuhiko; Kitazato, Kaio; Klein, Ludger; Klimecki, Walter T; Klucken, Jochen; Knecht, Erwin; Ko, Ben C B; Koch, Jan C; Koga, Hiroshi; Koh, Jae-Young; Koh, Young Ho; Koike, Masato; Komatsu, Masaaki; Kominami, Eiki; Kong, Hee Jeong; Kong, Wei-Jia; Korolchuk, Viktor I; Kotake, Yaichiro; Koukourakis, Michael I; Kouri Flores, Juan B; Kovacs, Attila L; Kraft, Claudine; Krainc, Dimitri; Kramer, Helmut; Kretz-Remy, Carole; Krichevsky, Anna M; Kroemer, Guido; Kruger, Rejko; Krut, Oleg; Ktistakis, Nicholas T; Kuan, Chia-Yi; Kucharczyk, Roza; Kumar, Ashok; Kumar, Raj; Kumar, Sharad; Kundu, Mondira; Kung, Hsing-Jien; Kurz, Tino; Kwon, Ho Jeong; La Spada, Albert R; Lafont, Frank; Lamark, Trond; Landry, Jacques; Lane, Jon D; Lapaquette, Pierre; Laporte, Jocelyn F; Laszlo, Lajos; Lavandero, Sergio; Lavoie, Josee N; Layfield, Robert; Lazo, Pedro A; Le, Weidong; Le Cam, Laurent; Ledbetter, Daniel J; Lee, Alvin J X; Lee, Byung-Wan; Lee, Gyun Min; Lee, Jongdae; Lee, Ju-Hyun; Lee, Michael; Lee, Myung-Shik; Lee, Sug Hyung; Leeuwenburgh, Christiaan; Legembre, Patrick; Legouis, Renaud; Lehmann, Michael; Lei, Huan-Yao; Lei, Qun-Ying; Leib, David A; Leiro, Jose; Lemasters, John J; Lemoine, Antoinette; Lesniak, Maciej S; Lev, Dina; Levenson, Victor V; Levine, Beth; Levy, Efrat; Li, Faqiang; Li, Jun-Lin; Li, Lian; Li, Sheng; Li, Weijie; Li, Xue-Jun; Li, Yan-bo; Li, Yi-Ping; Liang, Chengyu; Liang, Qiangrong; Liao, Yung-Feng; Liberski, Pawel P; Lieberman, Andrew; Lim, Hyunjung J; Lim, Kah-Leong; Lim, Kyu; Lin, Chiou-Feng; Lin, Fu-Cheng; Lin, Jian; Lin, Jiandie D; Lin, Kui; Lin, Wan-Wan; Lin, Weei-Chin; Lin, Yi-Ling; Linden, Rafael; Lingor, Paul; Lippincott-Schwartz, Jennifer; Lisanti, Michael P; Liton, Paloma B; Liu, Bo; Liu, Chun-Feng; Liu, Kaiyu; Liu, Leyuan; Liu, Qiong A; Liu, Wei; Liu, Young-Chau; Liu, Yule; Lockshin, Richard A; Lok, Chun-Nam; Lonial, Sagar; Loos, Benjamin; Lopez-Berestein, Gabriel; Lopez-Otin, Carlos; Lossi, Laura; Lotze, Michael T; Low, Peter; Lu, Binfeng; Lu, Bingwei; Lu, Bo; Lu, Zhen; Luciano, Frederic; Lukacs, Nicholas W; Lund, Anders H; Lynch-Day, Melinda A; Ma, Yong; Macian, Fernando; MacKeigan, Jeff P; Macleod, Kay F; Madeo, Frank; Maiuri, Luigi; Maiuri, Maria Chiara; Malagoli, Davide; Malicdan, May Christine V; Malorni, Walter; Man, Na; Mandelkow, Eva-Maria; Manon, Stephen; Manov, Irena; Mao, Kai; Mao, Xiang; Mao, Zixu; Marambaud, Philippe; Marazziti, Daniela; Marcel, Yves L; Marchbank, Katie; Marchetti, Piero; Marciniak, Stefan J; Marcondes, Mateus; Mardi, Mohsen; Marfe, Gabriella; Marino, Guillermo; Markaki, Maria; Marten, Mark R; Martin, Seamus J; Martinand-Mari, Camille; Martinet, Wim; Martinez-Vicente, Marta; Masini, Matilde; Matarrese, Paola; Matsuo, Saburo; Matteoni, Raffaele; Mayer, Andreas; Mazure, Nathalie M; McConkey, David J; McConnell, Melanie J; McDermott, Catherine; McDonald, Christine; McInerney, Gerald M; McKenna, Sharon L; McLaughlin, BethAnn; McLean, Pamela J; McMaster, Christopher R; McQuibban, G Angus; Meijer, Alfred J; Meisler, Miriam H; Melendez, Alicia; Melia, Thomas J; Melino, Gerry; Mena, Maria A; Menendez, Javier A; Menna-Barreto, Rubem F S; Menon, Manoj B; Menzies, Fiona M; Mercer, Carol A; Merighi, Adalberto; Merry, Diane E; Meschini, Stefania; Meyer, Christian G; Meyer, Thomas F; Miao, Chao-Yu; Miao, Jun-Ying; Michels, Paul A M; Michiels, Carine; Mijaljica, Dalibor; Milojkovic, Ana; Minucci, Saverio; Miracco, Clelia; Miranti, Cindy K; Mitroulis, Ioannis; Miyazawa, Keisuke; Mizushima, Noboru; Mograbi, Baharia; Mohseni, Simin; Molero, Xavier; Mollereau, Bertrand; Mollinedo, Faustino; Momoi, Takashi; Monastyrska, Iryna; Monick, Martha M; Monteiro, Mervyn J; Moore, Michael N; Mora, Rodrigo; Moreau, Kevin; Moreira, Paula I; Moriyasu, Yuji; Moscat, Jorge; Mostowy, Serge; Mottram, Jeremy C; Motyl, Tomasz; Moussa, Charbel E-H; Muller, Sylke; Muller, Sylviane; Munger, Karl; Munz, Christian; Murphy, Leon O; Murphy, Maureen E; Musaro, Antonio; Mysorekar, Indira; Nagata, Eiichiro; Nagata, Kazuhiro; Nahimana, Aimable; Nair, Usha; Nakagawa, Toshiyuki; Nakahira, Kiichi; Nakano, Hiroyasu; Nakatogawa, Hitoshi; Nanjundan, Meera; Naqvi, Naweed I; Narendra, Derek P; Narita, Masashi; Navarro, Miguel; Nawrocki, Steffan T; Nazarko, Taras Y; Nemchenko, Andriy; Netea, Mihai G; Neufeld, Thomas P; Ney, Paul A; Nezis, Ioannis P; Nguyen, Huu Phuc; Nie, Daotai; Nishino, Ichizo; Nislow, Corey; Nixon, Ralph A; Noda, Takeshi; Noegel, Angelika A; Nogalska, Anna; Noguchi, Satoru; Notterpek, Lucia; Novak, Ivana; Nozaki, Tomoyoshi; Nukina, Nobuyuki; Nurnberger, Thorsten; Nyfeler, Beat; Obara, Keisuke; Oberley, Terry D; Oddo, Salvatore; Ogawa, Michinaga; Ohashi, Toya; Okamoto, Koji; Oleinick, Nancy L; Oliver, F Javier; Olsen, Laura J; Olsson, Stefan; Opota, Onya; Osborne, Timothy F; Ostrander, Gary K; Otsu, Kinya; Ou, Jing-hsiung James; Ouimet, Mireille; Overholtzer, Michael; Ozpolat, Bulent; Paganetti, Paolo; Pagnini, Ugo; Pallet, Nicolas; Palmer, Glen E; Palumbo, Camilla; Pan, Tianhong; Panaretakis, Theocharis; Pandey, Udai Bhan; Papackova, Zuzana; Papassideri, Issidora; Paris, Irmgard; Park, Junsoo; Park, Ohkmae K; Parys, Jan B; Parzych, Katherine R; Patschan, Susann; Patterson, Cam; Pattingre, Sophie; Pawelek, John M; Peng, Jianxin; Perlmutter, David H; Perrotta, Ida; Perry, George; Pervaiz, Shazib; Peter, Matthias; Peters, Godefridus J; Petersen, Morten; Petrovski, Goran; Phang, James M; Piacentini, Mauro; Pierre, Philippe; Pierrefite-Carle, Valerie; Pierron, Gerard; Pinkas-Kramarski, Ronit; Piras, Antonio; Piri, Natik; Platanias, Leonidas C; Poggeler, Stefanie; Poirot, Marc; Poletti, Angelo; Pous, Christian; Pozuelo-Rubio, Mercedes; Praetorius-Ibba, Mette; Prasad, Anil; Prescott, Mark; Priault, Muriel; Produit-Zengaffinen, Nathalie; Progulske-Fox, Ann; Proikas-Cezanne, Tassula; Przedborski, Serge; Przyklenk, Karin; Puertollano, Rosa; Puyal, Julien; Qian, Shu-Bing; Qin, Liang; Qin, Zheng-Hong; Quaggin, Susan E; Raben, Nina; Rabinowich, Hannah; Rabkin, Simon W; Rahman, Irfan; Rami, Abdelhaq; Ramm, Georg; Randall, Glenn; Randow, Felix; Rao, V Ashutosh; Rathmell, Jeffrey C; Ravikumar, Brinda; Ray, Swapan K; Reed, Bruce H; Reed, John C; Reggiori, Fulvio; Regnier-Vigouroux, Anne; Reichert, Andreas S; Reiners, John J Jr; Reiter, Russel J; Ren, Jun; Revuelta, Jose L; Rhodes, Christopher J; Ritis, Konstantinos; Rizzo, Elizete; Robbins, Jeffrey; Roberge, Michel; Roca, Hernan; Roccheri, Maria C; Rocchi, Stephane; Rodemann, H Peter; Rodriguez de Cordoba, Santiago; Rohrer, Barbel; Roninson, Igor B; Rosen, Kirill; Rost-Roszkowska, Magdalena M; Rouis, Mustapha; Rouschop, Kasper M A; Rovetta, Francesca; Rubin, Brian P; Rubinsztein, David C; Ruckdeschel, Klaus; Rucker, Edmund B 3rd; Rudich, Assaf; Rudolf, Emil; Ruiz-Opazo, Nelson; Russo, Rossella; Rusten, Tor Erik; Ryan, Kevin M; Ryter, Stefan W; Sabatini, David M; Sadoshima, Junichi; Saha, Tapas; Saitoh, Tatsuya; Sakagami, Hiroshi; Sakai, Yasuyoshi; Salekdeh, Ghasem Hoseini; Salomoni, Paolo; Salvaterra, Paul M; Salvesen, Guy; Salvioli, Rosa; Sanchez, Anthony M J; Sanchez-Alcazar, Jose A; Sanchez-Prieto, Ricardo; Sandri, Marco; Sankar, Uma; Sansanwal, Poonam; Santambrogio, Laura; Saran, Shweta; Sarkar, Sovan; Sarwal, Minnie; Sasakawa, Chihiro; Sasnauskiene, Ausra; Sass, Miklos; Sato, Ken; Sato, Miyuki; Schapira, Anthony H V; Scharl, Michael; Schatzl, Hermann M; Scheper, Wiep; Schiaffino, Stefano; Schneider, Claudio; Schneider, Marion E; Schneider-Stock, Regine; Schoenlein, Patricia V; Schorderet, Daniel F; 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In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
PMCID:3404883
PMID: 22966490
ISSN: 1554-8627
CID: 181862

Identification of hnRNPH1, NF45, and C14orf166 as novel host interacting partners of the mature hepatitis C virus core protein

Lee, Jun-Wei; Liao, Pao-Chi; Young, Kung-Chia; Chang, Christina L; Chen, Steve S L; Chang, Ting-Tsung; Lai, Ming-Derg; Wang, Shainn-Wei
The hepatitis C virus core protein (HCVc) forms the viral nucleocapsid and is involved in viral persistence and pathogenesis, possibly by interacting with host factors to modulate viral replication and cellular functions. Here, we identified 36 cellular protein candidates by one-dimensional SDS-PAGE and LC-MS/MS-based proteomics after affinity purification with HCVc174, a matured form of HCVc from HCV-1b genotype, tagged with biotin and calmodulin-binding peptide/protein A at N- and C-termini, respectively. By pull-down and confocal imaging techniques, we confirmed that heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1), nuclear factor 45 (NF45), and C14orf166 are novel HCVc174-interacting host proteins, known to participate in mRNA metabolism, gene regulation, and microtubule organization, respectively. Unlike the other 2 proteins, NF45 interacted with HCVc174 in an RNA-dependent manner. These 3 proteins colocalized with ectopic HCVc-1b in both the cytoplasm and nucleus, which demonstrated their spatial interaction with naturally translocated HCVc174 after HCVc biogenesis. Such colocalization, however, shifted to the cytoplasm in cells with replicating virus of 1b or 2a genotype, indicating that active viral replication confined these interacting proteins in the cytoplasm. Collectively, our findings suggest that spatial interactions of hnRNPH1, NF45, and C14orf166 with HCVc174 likely modulate HCV or cellular functions during acute and chronic HCV infection.
PMID: 21823664
ISSN: 1535-3907
CID: 5392112

Autophagy: a novel guardian of HCV against innate immune response

Ke, Po-Yuan; Chen, Steve S-L
Autophagy is an evolutionarily conserved process that catabolizes intracellular components and maintains cellular homeostasis. Autophagy involves the sequestration of cytoplasmic content within a double-membraned autophagosome, and the fusion of the autophagosome with a lysosome to form an autolysosome for subsequent degradation (Fig. 1A). Autophagy plays a pivotal role in various aspects of cellular responses to stresses, such as nutrient deprivation, damaged organelles, aggregated proteins, exposure to endoplasmic reticulum (ER) stress and pathogen infections. Virus infection often leads to ER stress and induction of the unfolded protein response (UPR). Recent studies reveal that virus-induced UPR may activate autophagy to support the virus life cycle. However, the exact roles of the UPR and autophagy in host cell-virus interactions are still enigmatic.
PMID: 21242722
ISSN: 1554-8635
CID: 5392122