Restricted replication of herpes simplex virus type 1 in murine embryonal carcinoma cells.
Herpes simplex virus type 1 (HSV-1) has a broad host range but the KOS strain of HSV-1 did not replicate efficiently in murine embryonal carcinoma (EC) cells. The yield of infectious HSV-1 from EC cells was 100- to 1000-fold lower than that from fibroblast cell lines of mouse, monkey or human origin. The thymidine kinase (TK) gene of HSV-1 is expressed early during the infectious cycle. The levels of TK mRNA and of TK activity in infected EC cells were only two- to threefold lower than levels from infected fibroblast cells. Infected EC cells supported replication of about half as much HSV-1 DNA as did fibroblast cells. The reduced yield of infectious virus was consistent with a paucity of virions in infected EC cells examined by electron microscopy, suggesting a major block late during the HSV-1 infectious cycle. We isolated a variant strain of HSV-1, called KOSEC, which replicated as efficiently in EC cells as in mouse fibroblasts. KOSEC infected EC and fibroblast cells, synthesized more TK mRNA, more TK enzyme, and more HSV-1 DNA than did the same cells infected with the KOS stain. Both HSV-1 strains induced similar levels of synthesis of gD, an early viral glycoprotein. By co-infection of EC cells with the KOS and KOSEC virus, both the elevated virus yield and the elevated TK synthesis seen in KOSEC-infected cells appeared to be recessive. Apparently a viral mutation that affects expression of some early viral functions can also overcome the EC cell restriction to HSV-1 replication.
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004261:DNA Replication; D005347:Fibroblasts / Q000378:metabolism; D005816:Genetic Complementation Test; D006801:Humans; D007739:L Cells / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology*; D013724:Teratoma / Q000378:metabolism*; D013937:Thymidine Kinase / Q000096:biosynthesis; D014709:Vero Cells / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis; D014776:Virus Cultivation; D014779:Virus Replication
D014764:Viral Proteins; D013937:Thymidine Kinase