TRANSCRIPTION FACTORS INTERACTING WITH HERPES-SIMPLEX VIRUS ALPHA-GENE PROMOTERS IN SENSORY NEURONS

Interference with VP16-mediated activation of herpes virus immediate-e arly (or alpha) genes is thought to be the major cause of establishing viral latency in sensory neurons. This could be brought about by lack of a key activating transcription factor(s) or active repression, In this study we find that sensory neurons express all important componen ts for VP16-mediated alpha gene induction, such as the POU transcripti on factor Oct-1, host cell factor (HCF) and GABP alpha/beta, However, Oct-1 and GABP alpha/beta are only present at low levels and the VP16- induced complex (VIC) appears different, We do not find protein expres sion of the transcription factor Oct-2, implicated by others as an alp ha gene repressor, The POU factor N-Oct3 (Brn 2 or POU3F2) is also pre sent in sensory neurons and binds viral TAATGARAT motifs with higher a ffinity than Oct-1, indicating that it may be a candidate repressor fo r competitive binding to TAATGARAT motifs, When transfected into HeLa cells, where Oct-1 and GABP alpha/beta are highly abundant, N-Oct3 rep resses model promoters with multimerized TAATGARAT motifs, but fails t o repress complete a gene promoters, Taken together our findings sugge st that modulation of alpha gene promoters could contribute to viral l atency when low concentrations of the activating transcription factors Oct-1 and GABP alpha/beta prevail, Our data, however, refute the noti on that competing Oct factors are able to block ex gene transcription to achieve viral latency.