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HIV-1 exploits the Fanconi anemia pathway for viral DNA integration.

ABSTRACT: 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.

SUBMITTER: Fu S

PROVIDER: S-EPMC9250337 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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HIV-1 exploits the Fanconi anemia pathway for viral DNA integration.

Fu Shaozu S Phan An Thanh AT Mao Dexin D Wang Xinlu X Gao Guangxia G Goff Stephen P SP Zhu Yiping Y

Cell reports 20220501 8

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 pro ...[more]

PMID: 35613597

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