THE CDNA OF U(L)15, A HIGHLY CONSERVED HERPES-SIMPLEX VIRUS-1 GENE, EFFECTIVELY REPLACES THE 2 EXONS OF THE WILD-TYPE VIRUS

The U(L)15 gene of herpes simplex virus 1 (HSV-1) is encoded by two or more exons in all herpesvirus genomes sequenced to date. The U(L)15 coding region is highly conserved, and the intron invariably encodes other genes transcribed antisense to the U(L)15 coding region. Previously we reported that we deleted the intron domain encoding U(L)16 but were unable to delete U(L)15 (J. D. Baines and B. Roizman, J. Virol. 65:938-944, 1991). Here we report that we replaced exon I of U(L)15 with an unspliced cDNA copy of U(L)15 in HSV-1 DNA and deleted 58% of the carboxyl-terminal sequences of the natural copy of exon II, including the polyadenylation signal. The yields of infectious virus obtained upon infection with viruses containing the cDNA copy of U(L)15 were similar to those of an isogenic virus with a wild-type U(L)15 gene. We therefore conclude that the separation of the two exons of U(L)15 by an intron encoding two genes is not essential for the replication of HSV, at least in cell culture.