Interaction of the betapapillomavirus E2 tethering protein with mitotic chromosomes.
During persistent papillomavirus infection, the viral E2 protein tethers the viral genome to the host cell chromosomes, ensuring maintenance and segregation of the viral genome during cell division. However, E2 proteins from different papillomaviruses interact with distinct chromosomal regions and targets. The tethering mechanism has been best characterized for bovine papillomavirus type 1 (BPV1), where the E2 protein tethers the viral genome to mitotic chromosomes in complex with the cellular bromodomain protein, Brd4. In contrast, the betapapillomavirus human papillomavirus type 8 (HPV8) E2 protein binds to the repeated ribosomal DNA genes that are found on the short arm of human acrocentric chromosomes. In this study, we show that a short 16-amino-acid peptide from the hinge region and the C-terminal DNA binding domain of HPV8 E2 are necessary and sufficient for interaction with mitotic chromosomes. This 16-amino-acid region contains an RXXS motif that is highly conserved among betapapillomaviruses, and both arginine 250 and serine 253 residues within this motif are required for mitotic chromosome binding. The HPV8 E2 proteins are highly phosphorylated, and serine 253 is a site of phosphorylation. The HPV8 E2 chromosome binding sequence also has sequence similarity with chromosome binding regions in the gammaherpesvirus EBNA and LANA tethering proteins.
Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
Vandana
V
Sekhar
Shawna C
SC
Reed
Alison A
AA
McBride
D020816:Amino Acid Motifs; D052686:Betapapillomavirus / Q000235:genetics*; D001665:Binding Sites; D018797:Cell Cycle Proteins; D002877:Chromosomes, Human / Q000378:metabolism*; D017124:Conserved Sequence; D016679:Genome, Viral; D006801:Humans; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D010766:Phosphorylation; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D000092468:Bromodomain Containing Proteins
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D015534:Trans-Activators; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C468298:oncogene protein E2, Human papillomavirus type 8