INHIBITION OF HERPES-SIMPLEX VIRUS-INFECTION BY ECTOPIC EXPRESSION OFNEURONAL SPLICE VARIANTS OF THE OCT-2 TRANSCRIPTION FACTOR

Herpes simplex virus (HSV) is capable of lytic replication in most cel ls, such replication in epithelial cells resulting in the mucocutaneou s lesions observed following in vivo infection. In addition however, t he virus also establishes asymptomatic latent infections in sensory ne urons which serve as a reservoir for further cycles of peripheral lyti c infections. These latent infections are dependent upon the inhibitio n of viral immediate-early (IE) gene expression via the octamer-relate d TAATGARAT motif in the IE promoters resulting in the failure of the viral lytic cycle. Here we show that the ectopic expression of neurona l isoforms of the octamer/TAATGARAT-binding transcription factor Oct-2 in permissive BHK cells represses IE gene expression following HSV in fection and inhibits the viral lytic cycle whereas the B lymphocyte is oform of Oct-2 does not have this effect. These results suggest that t he neuronal isoforms of Oct-2 play a critical role in rendering neuron al cells non-permissive for the viral lytic cycle thereby allowing the establishment of latent infection. Moreover, this is the first time t hat the ectopic expression of a cellular transcription factor has been shown to inhibit infection with any virus, raising the possibility of therapeutically inhibiting lytic viral infections by inducing such ec topic expression.