Abstract

Herpes simplex virus type 1 establishes a latent infection in the sensory neurons of the peripheral nervous system of humans. Although about 80 genes are expressed during the lytic cycle of the virus infection, essentially only one gene is expressed during the latent cycle. This gene is known as the latency-associated transcript (LAT), and it appears to play a role in the latency cycle through an anti-apoptotic function in the 5' end of the gene and miRNA encoded along the length of the transcript which downregulate some of the viral immediate-early gene products. The LAT gene is about 8.3 kb long and consists of two exons separated by an unusual intron. The intron between the exons consists of two nested introns. This arrangement of introns has been called a twintron. Furthermore, the larger (2 kb) intron has been shown to be very stable. In this study, we measure the stability of the shorter 1.5-kb nested intron and find its half-life is similar to the longer intron. This was achieved by deleting the 0.5-kb overlapping intron from a plasmid construct designed to express the LAT transcript from a tet-inducible promoter and measuring the half-life of the 1.5-kb intron in tissue culture cells. This finding supports the hypothesis that it is the common branch-point region of these nested introns that is responsible for their stability.

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