Hormone response element in SV40 late promoter directly affects synthesis of early as well as late viral RNAs

We previously demonstrated that the presence of a hormone response element surrounding the transcription initiation site of the SV40 major late promoter (+1 HIRE) confers a replication advantage to the virus in a cell-type-specific manner. We determine here the mechanism by which the +1 HIRE confers this advantage by analyzing in detail the various stages of the viral life cycle of wild-type versus a +1 HIRE mutant in MA-134 cells. We show that the mutant overexpresses late genes at the expense of early genes at early times after infection. This initial underproduction of early RNA leads, subsequently, to an underproduction of large T-antigen, viral DNA, and infectious virions. We conclude that the +1 HIRE is necessary for the proper initial regulation of transcription from the early as well as late promoter so the cascade of subsequent events can be executed for the optimal production of virions. (C) 2002 Elsevier science (USA).