Control of viral replication and transcription by the papillomavirus E8^E2 protein.
Human papillomaviruses have adjusted their replication levels to the differentiation state of the infected keratinocyte. PV genomes replicate in undifferentiated cells at low levels and to high levels in differentiated cells. Genome replication requires the viral E1 helicase and the viral E2 transcription/replication activator. The limited replication in undifferentiated cells is predominantly due to the expression of the highly conserved E8^E2 viral repressor protein, which is a fusion between E8 and the C-terminal half of the E2 protein. E8^E2 is a sequence-specific DNA binding protein that inhibits viral gene expression and viral genome replication. The E8 domain is required for repression activities, which are mainly due to the interaction with cellular NCoR/SMRT corepressor complexes. In the case of HPV16, the most carcinogenic HPV type, E8^E2 not only limits genome replication in undifferentiated cells but also productive replication in differentiated epithelium. E8^E2 is expressed from a separate promoter that is controlled by unknown cellular factors and the viral transcription and replication regulators E1, E2 and E8^E2. In summary, E8^E2 is an important negative regulator whose levels may be critical for the outcome of HPV infections.
University Hospital Tuebingen, Institute for Medical Virology and Epidemiology of Viral Diseases, Division of Experimental Virology, Elfriede-Aulhorn-Str. 6, 72076, Tuebingen, Germany.
Marcel
M
Dreer
University Hospital Tuebingen, Institute for Medical Virology and Epidemiology of Viral Diseases, Division of Experimental Virology, Elfriede-Aulhorn-Str. 6, 72076, Tuebingen, Germany.
Saskia
S
van de Poel
University Hospital Tuebingen, Institute for Medical Virology and Epidemiology of Viral Diseases, Division of Experimental Virology, Elfriede-Aulhorn-Str. 6, 72076, Tuebingen, Germany.
Frank
F
Stubenrauch
D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D054884:Host-Pathogen Interactions; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000821:virology; D056971:Nuclear Receptor Co-Repressor 1 / Q000235:genetics / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D014779:Virus Replication
D004268:DNA-Binding Proteins; C093478:E1 protein, Human papillomavirus 16; C054855:E2 protein, Human papillomavirus type 16; C539127:NCOR1 protein, human; D056971:Nuclear Receptor Co-Repressor 1; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral
E2; E8^E2; HPV; NCOR; Papillomavirus; Replication; Repressor; SMRT