The DNA repair genes XPB and XPD defend cells from retroviral infection.
Reverse transcription of retroviral RNA genomes produce a double-stranded linear cDNA molecule. A host degradation system prevents a majority of the cDNA molecules from completing the obligatory genomic integration necessary for pathogenesis. We demonstrate that the human TFIIH complex proteins XPB (ERCC3) and XPD (ERCC2) play a principal role in the degradation of retroviral cDNA. DNA repair-deficient XPB and XPD mutant cell lines exhibited an increase in transduction efficiency by both HIV- and Moloney murine leukemia virus-based retroviral vectors. Replicating Moloney murine leukemia virus viral production was greater in XPB or XPD mutant cells but not XPA mutant cells. Quantitative PCR showed an increase in total cDNA molecules, integrated provirus, and 2LTR circles in XPB and XPD mutant cells. In the presence of a reverse transcription inhibitor, the HIV cDNA appeared more stable in mutant XPB or XPD cells. These studies implicate the nuclear DNA repair proteins XPB and XPD in a cellular defense against retroviral infection.
Department of Molecular Virology, and Ohio State University Comprehensive Cancer Center, Ohio State University College of Medicine, Columbus, OH 43210, USA.
Kristine
K
Yoder
Alain
A
Sarasin
Kenneth
K
Kraemer
Michael
M
McIlhatton
Frederic
F
Bushman
Richard
R
Fishel
D000818:Animals; D002460:Cell Line; D004265:DNA Helicases / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics; D018076:DNA, Complementary / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006678:HIV / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014779:Virus Replication; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics / Q000502:physiology*
D018076:DNA, Complementary; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C072022:XPBC-ERCC-3 protein; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein