title: XPB mediated retroviral cDNA degradation coincides with entry to the nucleus.
abstract: Retroviruses must integrate their cDNA to a host chromosome, but a significant fraction of retroviral cDNA is degraded before integration. XPB and XPD are part of the TFIIH complex which mediates basal transcription and DNA nucleotide excision repair. Retroviral infection increases when XPB or XPD are mutant. Here we show that inhibition of mRNA or protein synthesis does not affect HIV cDNA accumulation suggesting that TFIIH transcription activity is not required for degradation. Other host factors implicated in the stability of cDNA are not components of the XPB and XPD degradation pathway. Although an increase of retroviral cDNA in XPB or XPD mutant cells correlates with an increase of integrated provirus, the integration efficiency of pre-integration complexes is unaffected. Finally, HIV and MMLV cDNA degradation appears to coincide with nuclear import. These results suggest that TFIIH mediated cDNA degradation is a nuclear host defense against retroviral infection.
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University Medical Center, Columbus, OH 43210, USA. yoder.176@osu.edu
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Yoder
authors.forename: William
authors.initials: W
authors.lastname: Roddick
authors.forename: Pia
authors.initials: P
authors.lastname: Hoellerbauer
authors.forename: Richard
authors.initials: R
authors.lastname: Fishel
mesh_terms: D021581:Active Transport, Cell Nucleus; D002478:Cells, Cultured; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006678:HIV / Q000502:physiology*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000502:physiology; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D016662:Virus Integration; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D050505:Mutant Proteins; C072022:XPBC-ERCC-3 protein; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human