Abstract
The ability of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and human cytomegalovirus (HCMV) to replicate, synthesize virus DNA, and stimulate incorporation of [ 3H]thymidine into cell DNA in isolated adult rat hepatocytes has been studied. HSV-1 replicated in these cells by 22–30 hr postinfection (p.i.) to yields that exceeded the input amount of virus. In contrast, HSV-2 replicated poorly. Replication of HSV-2 was unaltered whether hepatocyte monolayers were prepared by plating directly on plastic dishes or plating on a collagen gel/nylon mesh substratum. After HCMV infection, no cytopathology was evident and virus was not detectable by plaque titration. HCMV infection stimulated incorporation of [ 3H]thymidine into hepatocyte DNA but HCMV DNA was not detectable. Significant levels of HSV-1 DNA were synthesized by 23 hr p.i. with HSV-1 but incorporation of the radiolabel into the cell DNA peak was reduced. In contrast, HSV-2 showed not only a significant level of virus DNA, but incorporation of [ 3H]thymidine into the cell DNA peak, was markedly increased by 23 hr p.i. over that in mock-infected cultures. HSV-2-induced stimulation of radiolabel incorporation into hepatocyte DNA was: (i) eliminated when HSV-2 was heat inactivated for 2 hr at 56°, (ii) dependent on virus multiplicity, and (iii) maximal at 22–25 hr p.i. with 10 PFU of HSV-2 per cell. Autoradiography of HSV-2-infected cultures revealed that at 10–13 hr p.i. 3870 of the cells in the hepatocyte monolayer were labeled. We conclude that nonproliferating differentiated hepatocytes: (i) can support the synthesis of HSV-1 and HSV-2 DNAs, (ii) can support the replication of HSV-1 and HSV-2, and (iii) show increased incorporation of [ 3H]thymidine into hepatocyte DNA after infection with either HCMV or HSV-2. It is of particular interest that in HSV-2 infection of hepatocytes in which virus DNA is made, incorporation of label into host DNA is not suppressed but is stimulated.
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