Trans activation of transcription by herpes virus products: requirement for two HSV-1 immediate-early polypeptides for maximum activity

Abstract

The transcriptional programme of the herpes viruses is organised into three principal phases. The immediate-early (IE) genes are the first to be transcribed, by the pre-existing host RNA polymerase II, and their promoters are strongly stimulated by a polypeptide component of the virus particle. The E and L gene promoters become active only after the appearance of IE gene products. Genetic and biochemical evidence has shown that the HSV-1 IE polypeptide Vmw175 (ICP 4) is essential for the trans activation of HSV early promoters, but the role of none of the other four IE gene products was known. This paper describes functional tests that show, by co-transfection of recombinant plasmids into HeLa cells, that (i) Vmw175 alone can activate an HSV-1 E gene promoter, (ii) the four other HSV-1 IE gene products by themselves are unable to activate transcription, (iii) the combination of Vmw175 plus the product of IE gene 1, Vmw110 (ICP 0), is a much better activator than Vmw175 alone, (iv) cloned IE gene products of human cytomegalovirus (CMV), varicella-zoseter virus (VZV) and pseudorabies virus (PRV) can also activate transcription from an HSV-1 early promoter, and (v) this activation also occurs with cellular promoters.