Faculty Bibliography

Inoculation of human FS-4 cells with Newcastle disease virus (NDV) resulted in the induction of two distinct interferon responses, one that peaked at about 5 hr (early response) and one that reached a maximum between 10 to 24 hr after inoculation (second response). The early interferon response was enhanced by previous treatment of the cells with interferon (priming), whereas the second response decreased after interferon treatment in a dose-dependent manner. The early response diminished with decreasing multiplicities of infection, the magnitude of the second response in unprimed cells was relatively independent of the dose of NDV employed. The early interferon response was sensitive to inhibition by actinomycin D for only 1 hr after inoculation. In marked contrast, the second response remained sensitive to inhibition by actinomycin D until 12 hr after inoculation. The ability of NDV to induce the second response was greatly diminished by irradiation of the virus with ultraviolet light or by its treatment with hydroxylamine, whereas the ability to stimulate the early response was relatively resistant to these virus-inactivating treatments. Treatment of NDV with hydroxylamine abolished the virus to induce the second response at the same rate as it destroyed infectivity. The results suggest the existence of at least two distinct mechanisms of interferon induction by NDV; the early response is triggered either by a virion component or by a product of primary transcription, whereas induction of the second response requires the expression of some functions of the virus not needed for triggering the early response

Human FS-4 cells were exposed to human fibroblast interferon for various times and further incubated in the absence of interferon until challenged with vesicular stomatitis virus. Addition of antibody to fibroblast interferon at the time of removal of interferon did not alter the development of the antiviral state. If cells were exposed to interferon for 45 min at either 0 or 37 degrees C, they developed resistance upon subsequent incubation at 37 degrees C. However, less resistance developed if the cells were initially incubated at 0 degrees C. Our results indicate that a single interaction of fibroblast interferon with susceptible cells, either at 0 or 37 degrees C, is sufficient for the subsequent development of an antiviral state, at least in the short term experiment. The kinetics of development of the antiviral state were compared with fibroblast and leukocyte interferon. The rise in the degree of antiviral resistance was steeper and maximal levels of resistance were reached sooner when FS-4 cells were incubated with increasing concentrations of fibroblast interferon than with leukocyte interferon. This suggests a greater affinity of fibroblast interferon for these cells

DRB is an inhibitor of heterogeneous nuclear RNA (hnRNA) and messenger RNA (MRNA) synthesis. The effect of DRB on interferon production stimulated by Newcastle disease virus (NDV) in the human FS-4 cells was studied. Interferon production in cells primed by treatment with interferon was markedly enhanced (superinduced) in the presence of DRB. This superinduction was essentially due to an inhibition of the rapid decline (shutoff) of interferon production observed in primed cells not treated with DRB. Continuous presence of DRB was required for maximal superinduction. In this and other respects the interferon response induced by NDV in primed cells resembled poly(I). poly(C)-induced interferon production. In contrast interferon production in cells not primed with interferon was virtually abolished by DRB treatment. Since neither virus specific RNA synthesis nor virus replication were significantly affected by DRB, the inhibition of interferon production is likely to result from the inhibitory action of DRB on a cellular, rather than viral, function. Apparently some differences exist in the synthesis or processing of the mRNAs for interferons in primed and unprimed cells and these determine the different sensitivities of these two responses to DRB