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J Gen Virol 68 (1987), 555-568; DOI 10.1099/0022-1317-68-2-555
© 1987 Society for General Microbiology

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Restricted Replication of Herpes Simplex Virus Type 1 in Murine Embryonal Carcinoma Cells

John C. Bell{dagger}, Jose Campione-Piccardo{ddagger}, Jane Craig, Kenneth R. Reuhl1 and Michael W. McBurney

Department of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5
and1 Ecotoxicology Group, National Research Council of Canada, Ottawa, Ontario K1A 0R6, Canada

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.

Keywords: HSV-1, replication, restricted, EC cells

{dagger} Present address: Department of Biochemistry, McGill University, 3655 Drummond Street, Montreal H3G 1Y6, Canada.

{ddagger} Present address: Laboratory Centre for Disease Control, Health and Welfare Canada, Ottawa, Ontario K1A 0L2 Canada.

Received 23 April 1986; accepted 28 October 1986.





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Copyright © 1987 by the Society for General Microbiology.