Formation of non-infective herpesvirus particles in cultured cells treated with human interferon

Treatment of HeLa cells with human lymphoblastoid interferon [HuIFN-alpha(Ly)] induced an antiviral state that rendered the cells refractory to infection by herpes simplex virus type 1 (HSV-1), and the yield of infectious HSV-1 was reduced by 98%. Analysis of the mechanism of the anti-herpes action of IFN indicated that no gross inhibition of viral protein synthesis took place and late proteins appeared, although the synthesis of some of them was partially inhibited. No differences were apparent between the glycoproteins or phosphoproteins synthesized in control and IFN-treated HSV-1-infected HeLa cells. No inhibition of the formation of new virus particles from IFN-treated cells was evident as assessed by electron microscopy and biochemical analyses, although their infectivity was drastically reduced. These virions exhibited some differences in their content of a few proteins as determined by PAGE. Studies on the second infection cycle with virions obtained from IFN-treated cells suggested that they attached and penetrated HeLa cells but that their development was impaired, since no viral protein synthesis was observed during the second infection. Altogether these results do not support the idea that the molecular mechanism of action of human IFN against HSV-1 is mediated via the 2'-5' A system, or by the inactivation of initiation factors. Rather, they focus the problem of the anti-herpes action of IFN at the level of formation of defective virions.