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 prom oter of HSV-1 reduces the ability of LAT expression to be induced in t ransient assays, but has only a minimal impact on reactivation or the virus in in vitro systems. Here we show that a CRE mutation results in a significant reduction of adrenergically induced reactivation in viv o in the rabbit eye model. Spontaneous reactivation frequencies were a lso reduced. In addition, we demonstrate that this mutation has no eff ect on the amount of LAT expressed during latency when compared with t he 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. (C) 1997 Academic Press.