Anti-retroviral activity of TRIM5 alpha.
Human immunodeficiency virus type 1 (HIV-1) shows a very narrow host range limited to humans and chimpanzees. Experimentally, HIV-1 does not infect Old World monkeys, such as rhesus (Rh) and cynomolgus (CM) monkeys, and fails to replicate in activated CD4 positive T lymphocytes obtained from these monkeys. In contrast, simian immunodeficiency virus isolated from a macaque monkey (SIVmac) can replicate well in both Rh and CM. In 2004, tripartite motif 5 alpha (TRIM5 alpha) was identified as a host factor which plays an important role in the restricted host range of HIV-1. Rh and CM TRIM5 alpha restrict HIV-1 infection but not SIVmac, while in comparison, anti-viral activity of human TRIM5 alpha against those viruses is very weak. TRIM5 alpha consists of the RING, B-box 2, coiled-coil and SPRY (B30.2) domains. The RING domain is frequently found in E3 ubiquitin ligase and TRIM5 alpha is degraded via the ubiquitin-proteasome pathway during HIV-1 restriction. TRIM5 alpha recognises the multimerised capsid (viral core) of an incoming virus by its alpha-isoform specific SPRY domain and is believed to be involved in innate immunity to control retroviral infection. Differences in amino acid sequences in the SPRY domain of TRIM5 alpha of different monkey species were found to affect species-specific restriction of retrovirus infection, while differences in amino acid sequences in the viral capsid protein determine viral sensitivity to restriction. Accurate structural analysis of the binding surface between the viral capsid protein and TRIM5 alpha SPRY is thus required for the development of new antiretroviral drugs that enhance anti-HIV-1 activity of human TRIM5 alpha.
Nakayama
Emi E
EE
Department of Viral Infections, Research Institute for Microbial Disease, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. emien@biken.osaka-u.ac.jp
Shioda
Tatsuo
T
D000818:Animals; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008954:Models, Biological; D008958:Models, Molecular; D050506:Mutant Chimeric Proteins / Q000276:immunology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D050506:Mutant Chimeric Proteins; D011506:Proteins; C526560:TRIM5-cyclophilin A protein, Macaca nemestrina; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases