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Interference with VP16-mediated activation of herpes virus immediate-early (or α) 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 factors) or active repression. In this study we find that sensory neurons express all important components for VP16-mediated α gene induction, such as the POU transcription factor Oct-1, host cell factor (HCF) and GABPα/β. However, Oct-1 and GABPα/β are only present at low levels and the VP16-induced complex (VIC) appears different. We do not find protein expression of the transcription factor Oct-2, implicated by others as an α gene repressor. The POU factor N-Oct3 (Brn 2 or POU3F2) is also present in sensory neurons and binds viral TAATGARAT motifs with higher affinity than Oct-1, Indicating that It may be a candidate repressor for competitive binding to TAATGARAT motifs. When transfected into HeLa cells, where Oct-1 and GABPα/β are highly abundant, N-Oct3 represses model promoters with murtimerlzed TAATGARAT motifs, but fails to repress complete α gene promoters. Taken together our findings suggest that modulation of α gene promoters could contribute to viral latency when low concentrations of the activating transcription factors Oct-1 and GABPα/β prevail. Our data, however, refute the notion that competing Oct factors are able to block α gene transcription to achieve viral latency.