title: Variations in the association of papillomavirus E2 proteins with mitotic chromosomes.
abstract: The E2 protein segregates episomal bovine papillomavirus (BPV) genomes to daughter cells by tethering them to mitotic chromosomes, thus ensuring equal distribution and retention of viral DNA. To date, only the BPV1 E2 protein has been shown to bind to mitotic chromosomes. We assessed the localization of 13 different animal and human E2 proteins from seven papillomavirus genera, and we show that most of them are stably bound to chromosomes throughout mitosis. Furthermore, in contrast to the random association of BPV1 E2 with mitotic chromosomes, several of these proteins appear to bind to more specific regions of mitotic chromosomes. Using human papillomavirus (HPV) type 8 E2, we show that this region is adjacent to centromeres/kinetochores. Therefore, E2 proteins from both HPV and animal papillomavirus bind to mitotic chromosomes, and there are variations in the specificity of this binding. Only the alpha-papillomavirus E2 proteins do not stably associate with mitotic chromatin throughout mitosis. These proteins closely associate with prophase chromosomes and bind to chromosomes in telophase but not in metaphase. However, extraction of mitotic cells before fixation results in alpha-E2 proteins binding to the pericentromeric region of metaphase chromosomes, as observed for HPV8 E2. We postulate that this is the authentic target of these E2 proteins but that additional factors or a specialized cellular environment is required to stabilize this association. Thus, E2-mediated tethering of viral genomes to mitotic chromosomes is a common strategy of papillomaviruses, but different viruses have evolved different variations of this theme.
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jaquelline G
authors.initials: JG
authors.lastname: Oliveira
authors.forename: Leremy A
authors.initials: LA
authors.lastname: Colf
authors.forename: Alison A
authors.initials: AA
authors.lastname: McBride
mesh_terms: D052688:Bovine papillomavirus 1 / Q000235:genetics; D002875:Chromosomes / Q000648:ultrastructure*; D003001:Cloning, Molecular; D003062:Codon; D004268:DNA-Binding Proteins / Q000737:chemistry; D000939:Epitopes / Q000737:chemistry; D005822:Genetic Vectors; D016679:Genome, Viral; D006801:Humans; D015151:Immunoblotting; D018386:Kinetochores / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008938:Mitosis; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry; D010802:Phylogeny; D010957:Plasmids / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D003062:Codon; D004268:DNA-Binding Proteins; C117355:E2 protein, Human papillomavirus type 11; C054855:E2 protein, Human papillomavirus type 16; C098597:E2 protein, Human papillomavirus type 31; D000939:Epitopes; D009856:Oncogene Proteins, Viral; D014764:Viral Proteins