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

Shaozu Fu, An Thanh Phan, Dexin Mao, Xinlu Wang, Guangxia Gao, Stephen P Goff, Yiping Zhu

Cell reports 2022 May 24

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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. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Shaozu Fu, An Thanh Phan, Dexin Mao, Xinlu Wang, Guangxia Gao, Stephen P Goff, Yiping Zhu. HIV-1 exploits the Fanconi anemia pathway for viral DNA integration. Cell reports. 2022 May 24;39(8):110840