Yoder, KE and Espeseth, A and Wang, XH and Fang, Q and Russo, MT and Lloyd, RS and Hazuda, D and Sobol, RW and Fishel, R
(2011)
The base excision repair pathway is required for efficient lentivirus integration.
PLoS ONE, 6 (3).
Abstract
An siRNA screen has identified several proteins throughout the base excision repair (BER) pathway of oxidative DNA damage as important for efficient HIV infection. The proteins identified included early repair factors such as the base damage recognition glycosylases OGG1 and MYH and the late repair factor POLß, implicating the entire BER pathway. Murine cells with deletions of the genes Ogg1, Myh, Neil1 and Polß recapitulate the defect of HIV infection in the absence of BER. Defective infection in the absence of BER proteins was also seen with the lentivirus FIV, but not the gammaretrovirus MMLV. BER proteins do not affect HIV infection through its accessory genes nor the central polypurine tract. HIV reverse transcription and nuclear entry appear unaffected by the absence of BER proteins. However, HIV integration to the host chromosome is reduced in the absence of BER proteins. Pre-integration complexes from BER deficient cell lines show reduced integration activity in vitro. Integration activity is restored by addition of recombinant BER protein POLß. Lentiviral infection and integration efficiency appears to depend on the presence of BER proteins. © 2011 Yoder et al.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID |
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Yoder, KE | | | | Espeseth, A | | | | Wang, XH | | | | Fang, Q | | | | Russo, MT | | | | Lloyd, RS | | | | Hazuda, D | | | | Sobol, RW | rws9@pitt.edu | RWS9 | | Fishel, R | | | |
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Centers: |
Other Centers, Institutes, Offices, or Units > Hillman Cancer Center Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute |
Date: |
28 March 2011 |
Date Type: |
Publication |
Journal or Publication Title: |
PLoS ONE |
Volume: |
6 |
Number: |
3 |
DOI or Unique Handle: |
10.1371/journal.pone.0017862 |
Schools and Programs: |
School of Public Health > Human Genetics School of Medicine > Pharmacology and Chemical Biology |
Refereed: |
Yes |
MeSH Headings: |
Active Transport, Cell Nucleus; Animals; Cell Line; Cell Nucleus--metabolism; Cell Survival; DNA Damage; DNA Repair--genetics; DNA, Complementary--genetics; DNA, Viral--genetics; Gene Deletion; HIV Infections--genetics; Humans; Lentivirus--physiology; Lentivirus Infections--genetics; Mice; Reverse Transcription--genetics; Signal Transduction--genetics; Time Factors; Virus Integration--genetics |
Other ID: |
NLM PMC3063173 |
PubMed Central ID: |
PMC3063173 |
PubMed ID: |
21448280 |
Date Deposited: |
30 Aug 2012 14:33 |
Last Modified: |
05 Feb 2019 16:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/13815 |
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