Journal
CELL REPORTS
Volume 39, Issue 8, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2022.110840
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Funding
- NCI [R01 CA 30488]
- Chinese Academy of Sciences [XDB29010206]
- National Natural Science Foundation of China [81921005]
- University of Rochester start-up fund
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HIV-1 infection activates the host cell's DNA repair pathway FA and utilizes FANCI-D2 protein for stable integration of viral DNA into the genome. Knockout of FANCI inhibits both the replication of HIV-1 and its DNA integration.
The integration of HIV-1 DNA into the host genome results in single-strand gaps and 2-nt overhangs at the ends of viral DNA, which must be repaired by cellular enzymes. The cellular factors responsible for the DNA damage repair in HIV-1 DNA integration have not yet been well defined. We report here that HIV-1 infection potently activates the Fanconi anemia (FA) DNA repair pathway, and the FA effector proteins FANCI-D2 bind to the C-terminal domain of HIV-1 integrase. Knockout of FANCI blocks productive viral DNA integration and inhibits the replication of HIV-1. Finally, we show that the knockout of DNA polymerases or flap nuclease downstream of FANCI-D2 reduces the levels of integrated HIV-1 DNA, suggesting these enzymes may be responsible for the repair of DNA damages induced by viral DNA integration. These experiments reveal that HIV-1 exploits the FA pathway for the stable integration of viral DNA into host genome.
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