Papillomavirus genome structure, expression, and post-transcriptional regulation.
Papillomaviruses are a group of small non-enveloped DNA tumor viruses whose infection usually causes benign epithelial lesions (warts). Certain types of HPVs, such as HPV-16, HPV-18, and HPV-31, have been recognized as causative agents of cervical cancer and anal cancer and their infections, which arise via sexual transmission, are associated with more than 95% of cervical cancer. Papillomaviruses infect keratinocytes in the basal layer of stratified squamous epithelia and replicate in the nucleus of infected keratinocytes in a differentiation-dependent manner. Viral gene expression in infected cells depends on cell differentiation and is tightly regulated at the transcriptional and post-transcriptional levels. A noteworthy feature of all papillomavirus transcripts is that they are transcribed as a bicistronic or polycistronic form containing two or more ORFs and are polyadenylated at either an early or late poly(A) site. In the past ten years, remarkable progress has been made in understanding how this complex viral gene expression is regulated at the level of transcription (such as via DNA methylation) and particularly post-transcription (including RNA splicing, polyadenylation, and translation). Current knowledge of papillomavirus mRNA structure and RNA processing has provided some clues on how to control viral oncogene expression. However, we still have little knowledge about which mRNAs are used to translate each viral protein. Continuing research on post-transcriptional regulation of papillomavirus infection will remain as a future focus to provide more insights into papillomavirus-host interactions, the virus life-cycle, and viral oncogenesis.
Zheng
Zhi-Ming
ZM
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. zhengt@exchange.nih.gov
Baker
Carl C
CC
D019175:DNA Methylation; D015967:Gene Expression Regulation, Viral; D016678:Genome; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000503:physiopathology; D034622:RNA Interference; D012326:RNA Splicing; D014158:Transcription, Genetic