Study of the E2 gene product of the cottontail rabbit papillomavirus reveals a common mechanism of transactivation among papillomaviruses

Abstract

The long control region (LCR) of the cottontail rabbit papillomavirus (CRPV) harbors a transcriptional promoter which can be transactivated, as reflected by cat gene expression, by cotransfection with plasmids which express the intact E2 open reading frame of CRPV, human papillomavirus type 18 (HPV18), and bovine papillomavirus type 1 (BPV1). The E2 protein of CRPV can also transactivate the LCRs of BPV1, HPV1, and HPV18 inserted in front of the cat gene in enhancer or promoter configuration. Competition experiments in vivo and binding studies with CRPV E2 protein synthesized in vitro suggest that the different E2 proteins transactivate transcription by a common mechanism involving binding to the same ACCG-CGGT target sequence. The C-terminal part of the protein is necessary for its DNA-binding function. Analysis of the transactivation data and of the LCR sequences of these four viruses suggests that the two cutaneous viruses (CRPV and BPV1) present a similar pattern of promoter regulation but that the activity of the promoters of genital human viruses is less dependent on E2 regulation and is at least partially regulated by cellular factors.