Formation of Non-infective Herpesvirus Particles in Cultured Cells Treated with Human Interferon

Abstract

Treatment of human cervical carcinoma 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 EM and biochemical analyses, although their infectivity was drastically reduced. These virions exhibited some differences in their content of a few proteins as determined by polyacrylamide gel electrophoresis. Studies on the 2nd 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 2nd infection. Evidently, the molecular mechanism of action of human IFN against HSV-1 is not mediated via the 2''-5'' A system, or by the inactivation of initiation factors. The problem of the anti-herpes action of IFN appears to focus at the level of formation of defective virions.