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HIV-1 exploits the Fanconi anemia pathway for viral 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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250337/ https://www.ncbi.nlm.nih.gov/pubmed/35613597 http://dx.doi.org/10.1016/j.celrep.2022.110840 |
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author | Fu, Shaozu Phan, An Thanh Mao, Dexin Wang, Xinlu Gao, Guangxia Goff, Stephen P. Zhu, Yiping |
author_facet | Fu, Shaozu Phan, An Thanh Mao, Dexin Wang, Xinlu Gao, Guangxia Goff, Stephen P. Zhu, Yiping |
author_sort | Fu, Shaozu |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9250337 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
spelling | pubmed-92503372022-07-02 HIV-1 exploits the Fanconi anemia pathway for viral DNA integration Fu, Shaozu Phan, An Thanh Mao, Dexin Wang, Xinlu Gao, Guangxia Goff, Stephen P. Zhu, Yiping Cell Rep Article 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. 2022-05-24 /pmc/articles/PMC9250337/ /pubmed/35613597 http://dx.doi.org/10.1016/j.celrep.2022.110840 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Fu, Shaozu Phan, An Thanh Mao, Dexin Wang, Xinlu Gao, Guangxia Goff, Stephen P. Zhu, Yiping HIV-1 exploits the Fanconi anemia pathway for viral DNA integration |
title | HIV-1 exploits the Fanconi anemia pathway for viral DNA integration |
title_full | HIV-1 exploits the Fanconi anemia pathway for viral DNA integration |
title_fullStr | HIV-1 exploits the Fanconi anemia pathway for viral DNA integration |
title_full_unstemmed | HIV-1 exploits the Fanconi anemia pathway for viral DNA integration |
title_short | HIV-1 exploits the Fanconi anemia pathway for viral DNA integration |
title_sort | hiv-1 exploits the fanconi anemia pathway for viral dna integration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250337/ https://www.ncbi.nlm.nih.gov/pubmed/35613597 http://dx.doi.org/10.1016/j.celrep.2022.110840 |
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