Expression of herpes simplex virus type 1 (HSV-1) latency-associated transcripts and transcripts affected by the deletion in avirulent mutant HFEM: evidence for a new class of HSV-1 genes.

During latent herpes simplex virus type 1 (HSV-1) infection in the trigeminal ganglia of mice, three virus-specific transcripts, 2.0, 1.5, and 1.45 kilobases (kb), are detectable by Northern (RNA) blot analysis, but only the 2.0-kb transcript can be detected in HSV-1-infected tissue culture cells (J.G. Spivack and N. W. Fraser, J. Virol. 61:3842-3847, 1987). Since these latency-associated genes map to a diploid region of the genome, transcription from the deletion mutant HFEM, which contains only one complete copy of these genes, was investigated to determine the effect of gene dosage. The 4.1-kb HFEM deletion is located between the alpha genes ICP0 and ICP27. ICP0 mRNA and the 2.0-kb latency-associated transcript were present at normal levels during HFEM infection, but ICP27 mRNA and 0.9- and 1.1-kb transcripts that map near the deletion were not readily detectable. The levels of expression of one or more of these genes might be an important determinant of HSV-1 virulence in animal hosts. ICP27 mRNA accumulated when protein synthesis was inhibited before HFEM infection, implying that the deletion may affect ICP27 regulatory rather than coding elements. Expression of the 2.0-kb latency-associated transcript was characterized in infected CV-1 cells with metabolic inhibitors and strand-specific probes. On the basis of metabolic inhibitor studies, the gene encoding the 2.0-kb latency-associated transcript is not an alpha gene. During HSV-1 replication in infected tissue culture cells, the beta and gamma genes require the prior expression of alpha gene products. However, the latency-associated RNAs are expressed in the absence of detectable levels of alpha transcripts in latently infected mice. Thus, this latency-associated gene family appear to be regulated quite differently than alpha, beta, or gamma genes. For these reasons, and because the latency-associated genes may perform latent rather than replicative functions, we propose that they should be considered members of a new HSV-1 gene class, the lambda genes.