Cyclophilin A: an auxiliary but not necessary cofactor for TRIM5alpha restriction of HIV-1.
Cyclophilin A (Cyp A) binds the human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein and contributes to the early events in virus replication in some cells. The retroviral restriction factor TRIM5alpha can inhibit the early, post-entry phase of infection by associating with the incoming viral capsid. Cyp A has been proposed to prevent restriction factor binding in human cells, thus enhancing HIV-1 infectivity, and to potentiate restriction of HIV-1 in monkey cells. Here we show that the positive effects of Cyp A-CA binding on HIV-1 infectivity do not depend on human TRIM5alpha. Disruption of Cyp A binding to CA partially relieved the block to HIV-1 infection imposed by several TRIM5alpha variants, but Cyp A-CA binding was not absolutely required for TRIM5alpha antiviral activity. Inhibition of Cyp A function by cyclosporine significantly decreased the efficiency of TRIM5alpha-mediated restriction only when the restricted virus capsid interacted with Cyp A.
Stremlau
Matthew
M
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.
Song
Byeongwoon
B
Javanbakht
Hassan
H
Perron
Michel
M
Sodroski
Joseph
J
D000818:Animals; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D021984:Cyclophilin A / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D004285:Dogs; D020868:Gene Silencing; D015497:HIV-1 / Q000378:metabolism*; D000882:Haplorhini; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D011485:Protein Binding; D034741:RNA, Small Interfering; D016559:Tacrolimus / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014779:Virus Replication
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D034741:RNA, Small Interfering; D000070584:Tripartite Motif Proteins; D016572:Cyclosporine; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases; D021984:Cyclophilin A; D016559:Tacrolimus