Herpes Simplex Virus Thymidine Kinase Gene Expression Under Control of a Late Viral Promoter

Abstract

Herpes simplex virus (HSV) genes are expressed as at least three coordinately regulated gene classes during lytic infection. The delayed-early (DE) and late (L) genes require previous expression of one or more immediate-early (IE) genes for their own expression. The DE genes achieve maximal expression prior to viral DNA synthesis, while the L genes are maximally expressed after DNA replication (Honess and Roizman, 1974). A recombinant strain of HSV-1, X1N17, was used in this study to examine the effect of the gene promoter on the temporal expression of HSV genes. This virus carries a late viral promoter upstream from the coding sequences of a DE gene (thymidine kinase; TK). S1-mapping studies showed that X1N17-TK transcripts initiated under the control of the late promoter and accumulated with L class kinetics. However, the TK activity levels in X1N17-infected cells were not consistent with HSV late gene expression. Western blot analysis of infected cell proteins revealed that despite the high levels of X1N17-TK mRNA present in the cytoplasm late after infection, little TK polypeptide was being synthesized. This suggested that HSV genes are subject to post-transcriptional control mechanisms that modulate the efficiency of translation of viral transcripts. More specifically, it appears as though HSV-TK transcripts are not efficiently translated at late times in infected cells.