The herpes simplex virus 2 kb latency associated transcript (LAT) leader sequence allows efficient expression of downstream proteins which is enhanced in neuronal cells: possible function of LAT ORFs

Herpes simplex viruses (HSV)-1 and -2 enter latency in peripheral ganglia during which time a number of latency associated transcripts (LATs) are produced. The most abundant (2 kb) LAT contains ORFs of significant size which could play a role in latency. We hypothesized that the leader sequence of the 2 kb LAT might regulate expression of the LAT ORFs in neurons and mig ht th us enhance some aspect of the latency process. We show that constructs with the HSV-1 2 kb LAT leader sequence in front of a CAT gene are efficiently translated, with enhanced activity in cells of neuronal origin, but that from within a larger LAT-derived RNA from which 2 kb LATs are efficiently spliced, expression levels are low. Thus some further regulation of expression must occur if LAT ORFs are expressed in vivo. Experiments to test any regulatory function of the LAT ORFs in suppressing or stimulating immediate early (IE) gene expression during latency did not, however, show effects on IE promoters in cotransfection assays, nor on an early gene promoter which has recently been shown to be expressed early in reactivation.