Papillomavirus interaction with cellular chromatin.
High-risk human papillomavirus (HPV) infection is the primary risk factor for cervical cancer. HPVs establish persistent infection by maintaining their genomes as extrachromosomal elements (episomes) that replicate along with host DNA in infected cells. The productive life cycle of HPV is intimately tied to the differentiation program of host squamous epithelium. This review examines the involvement of host chromatin in multiple aspects of the papillomavirus life cycle and the malignant progression of infected host cells. Papillomavirus utilizes host mitotic chromosomes as vehicles for transmitting its genetic materials across the cell cycle. By hitchhiking on host mitotic chromosomes, the virus ensures accurate segregation of the replicated viral episomes to the daughter cells during host cell division. This strategy allows persistent maintenance of the viral episome in the infected cells. In the meantime, the virus subverts the host chromatin-remodeling factors to promote viral transcription and efficient propagation of viral genomes. By associating with the host chromatin, papillomavirus redirects the normal cellular control of chromatin to create a cellular environment conducive to both its own survival and malignant progression of host cells. Comprehensive understanding of HPV-host chromatin interaction will offer new insights into the HPV life cycle as well as chromatin regulation. This virus-host interaction will also provide a paradigm for investigating other episomal DNA tumor viruses that share a similar mechanism for interacting with host chromatin.
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. jianyou@mail.med.upenn.edu
Jianxin
J
You
D000818:Animals; D002843:Chromatin / Q000502:physiology*; D006801:Humans; D027383:Papillomaviridae / Q000502:physiology*; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology; D014779:Virus Replication / Q000502:physiology*
D002843:Chromatin