Antiretroviral potential of human tripartite motif-5 and related proteins.
TRIM5alpha is a potent inhibitor of infection by diverse retroviruses and is encoded by one of a large family of TRIM genes. We found that several TRIM motifs among a panel of selected human TRIM proteins (TRIM1, 5, 6, 18, 19, 21 22, 34) could inhibit infection when artificially targeted to an incoming HIV-1 capsid. Conversely, when ectopically expressed as authentic full-length proteins, most lacked activity against a panel of retroviruses. The exceptions were TRIM1, TRIM5 and TRIM34 proteins. Weak but specific inhibition of HIV-2/SIV(MAC) and EIAV by TRIM34 was noted, and human TRIM5alpha modestly, but specifically, inhibited an HIV-1 strain carrying a mutation in the cyclophilin binding loop (G89V). Restriction activity observed in ectopic expression assays was sometimes not detectable in corresponding RNAi-based knockdown experiments. However, endogenous owl monkey TRIMCyp potently inhibited an SIV(AGM) strain. Overall, sporadic examples of intrinsic antiretroviral activity exist in this panel of TRIM proteins.
Zhang
Fengwen
F
Aaron Diamond AIDS Research Center and the Laboratory of Retrovirology, the Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Hatziioannou
Theodora
T
Perez-Caballero
David
D
Derse
David
D
Bieniasz
Paul D
PD
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000090103:Antiviral Restriction Factors; D016645:Aotidae; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002415:Cats; D002460:Cell Line; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D016086:Lentivirus / Q000502:physiology*; D016180:Lentivirus Infections / Q000821:virology*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D016335:Zinc Fingers / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases