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Antiviral, Anticellular and Enzyme-inducing Activities of Interferons in RD-114 Cells

Memorial Sloan-Kettering Cancer Center and Sloan-Kettering Division of Graduate School of Medical Sciences, Cornell University, 1275 York Avenue, New York, N.Y. 10021, U.S.A.

RD-114 is a human sarcoma-derived cell line which is chronically infected with the RD-114 retrovirus. In a previous study, we found that treatment of these cells with human interferon- or human interferon- causes a marked inhibition of RD-114 virus production, but that the replication of exogenous vesicular stomatitis or encephalomyocarditis virus is not impaired. In the present study, we report that neither type of interferon has strong inhibitory effects on DNA synthesis or on multiplication of the cells. We also failed to detect a double-stranded RNA-dependent protein kinase activity in extracts of both interferon-treated and untreated cells. However, a low level of 2',5'-oligoadenylate [2,5(A)] synthetase activity was detectable in extracts of interferon-treated cells. 2,5(A)-dependent endonuclease L activity was detectable in extracts of both untreated and interferon-treated cells. This was probably responsible for the inhibition of protein synthesis observed upon introduction of 2,5(A) to RD-114 cells. In many cells, interferon has been found to induce synthesis of several proteins demonstrable by autoradiographic analysis of slab gels on which extracts of interferon-treated and radiolabelled cells are separated. Using a similar method, no such induced protein synthesis was detectable in interferon-treated RD-114 cells. Our results indicate that RD-114 cells are resistant to most known actions of interferons except for the antiretroviral action to which they are as sensitive as any other cell line.

Keywords: interferon resistance, antiviral action, differential actions

Received 16 March 1983; accepted 13 June 1983.