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Updated: Sep 22, 2025

Measurement of In Vitro Integration Activity of HIV-1 Preintegration Complexes
Published on: February 22, 2017
HIV-1 exploits the Fanconi anemia pathway for viral DNA integration
Shaozu Fu1, An Thanh Phan2, Dexin Mao2
1CAS Key Laboratory of Infection and Immunity, CAS Centre for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
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.
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