TRIM5alpha-independent anti-human immunodeficiency virus type 1 activity mediated by cyclophilin A in Old World monkey cells.
Cyclophilin A (CypA) is a peptidyl-prolyl isomerase that binds to the capsid protein of human immunodeficiency virus type 1 (HIV-1). TRIM5alpha is an antiretroviral factor influencing species-specific retroviral replication in Old World monkey (OWM) cells. In the study reported here, we investigated the role of CypA in anti-HIV-1 activity of OWM cells. Exogenous expression of CypA inhibited HIV-1 infection in OWM cells but not in human cells when the function of TRIM5alpha was suppressed by overexpression of dominant negative form of TRIM5alpha as well as by using RNA interference. This inhibitory action depended upon the interaction of the CypA moiety with HIV-1 capsid and disruption of CypA and capsid interaction by cyclosporine A enhanced the HIV-1 susceptibility of OWM cells even in the absence of functional TRIM5alpha. These results point to the presence of novel TRIM5alpha-independent anti-HIV-1 activity mediated by CypA in OWM cells.
Nakayama
Emi E
EE
Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita-Shi, Osaka, Japan. emien@biken.osaka-u.ac.jp
Shingai
Yasuhiro
Y
Kono
Ken
K
Shioda
Tatsuo
T
D000818:Animals; D002460:Cell Line; D002520:Cercopithecidae; D021984:Cyclophilin A / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D011506:Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D014774:Virulence; D014779:Virus Replication
D011506:Proteins; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases; D021984:Cyclophilin A