Rapid and selective shutoff of plasma protein production in herpes simplex virus type 2-infected hepatoma cells

Abstract

The effect of herpes simplex virus type 2 (HSV-2) infection of hepatoma McA-RH7777 cells on the production of alpha-fetoprotein (AFP) and several other secreted plasma proteins was examined. Cells infected with HSV-2 were labeled with [35S]methionine for various times postinfection (p.i.). Culture media and intracellular extracts were immunoprecipitated with plasma protein antibodies and examined by polyacrylamide gel electrophoresis. The relative levels of AFP and several other plasma proteins decreased substantially in infected cells compared with mock-treated controls; however, the level of at least one secreted plasma protein was unchanged after infection and the level of another increased after infection. Hybridization analyses with AFP cDNA showed that AFP RNA decreased to 43 and 30% of controls at 3.5 and 6.5 hr p.i., respectively. These observations were supported by the results of cell-free translation of isolated poly(A)-containing RNA. HSV-2 proteins were not detectable at times p.i. when AFP synthesis, secretion, and mRNA levels were significantly diminished. No decrease in AFP levels was observed in cells infected with ultraviolet-irradiated virus. We conclude that HSV-2 infection of McA-RH7777 cells leads to a rapid decrease in synthesis and secretion of specific plasma proteins which is apparent, at least for AFP, at the level of mRNA. This shutoff is not common to all McA-RH7777 cell proteins and, although seen early after infection, most likely requires the expression of a virus gene(s).