Mutagenesis of a cAMP response element within the latency-associated transcript promoter of HSV-1 reduces adrenergic reactivation.

Mutagenesis of a cyclic AMP response element (CRE) within the LAT promoter of HSV-1 reduces the ability of LAT expression to be induced in transient assays, but has only a minimal impact on reactivation of the virus in in vitro systems. Here we show that a CRE mutation results in a significant reduction of adrenergically induced reactivation in vivo in the rabbit eye model. Spontaneous reactivation frequencies were also reduced. In addition, we demonstrate that this mutation has no effect on the amount of LAT expressed during latency when compared with the parent, 17syn+, and the rescuant. These results indicate a greater effect of CRE on induced reactivation in vivo than in in vitro systems, but also suggest that the CRE in the LAT promoter is not autonomous in conducting the reactivation signal.