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

Cell Rep. 2022 May 24;39(8):110840. doi: 10.1016/j.celrep.2022.110840.


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.

Keywords: CP: Microbiology; Fanconi anemia DNA repair pathway; HIV-1; integration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Damage
  • DNA Repair
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • Fanconi Anemia Complementation Group D2 Protein / metabolism
  • Fanconi Anemia Complementation Group Proteins / genetics
  • Fanconi Anemia Complementation Group Proteins / metabolism
  • Fanconi Anemia* / genetics
  • Fanconi Anemia* / metabolism
  • HIV-1* / genetics
  • HIV-1* / metabolism
  • Humans
  • Ubiquitination


  • DNA, Viral
  • Fanconi Anemia Complementation Group D2 Protein
  • Fanconi Anemia Complementation Group Proteins

Supplementary concepts

  • Fanconi Anemia, Complementation Group I