title: Virus-specific effects of TRIM5α(rh) RING domain functions on restriction of retroviruses.
abstract: The tripartite motif protein TRIM5α restricts particular retrovirus infections by binding to the incoming capsid and inhibiting the early stage of virus infection. The TRIM5α RING domain exhibits E3 ubiquitin ligase activity and assists the higher-order association of TRIM5α dimers, which promotes capsid binding. We characterized a panel of RING domain mutants of the rhesus monkey TRIM5α (TRIM5α(rh)) protein. The RING domain function that significantly contributed to retroviral restriction depended upon the restricted virus. The E3 ubiquitin ligase activity of the RING domain contributes to the potency of HIV-1 restriction. Nonetheless, TRIM5α(rh) mutants without detectable E3 ubiquitin ligase activity still blocked reverse transcription and inhibited HIV-1 infection at a moderate level. When TRIM5α(rh) capsid binding was weakened by substitution with a less efficient B30.2/SPRY domain, the promotion of higher-order association by the RING domain was more important to HIV-1 restriction than its E3 ubiquitin ligase activity. For the restriction of N-tropic murine leukemia virus (N-MLV) and equine infectious anemia virus (EIAV) infection, promotion of higher-order association represented the major contribution of the RING domain. Thus, both identity of the target virus and the B30.2/SPRY domain-mediated affinity for the viral capsid determine the relative contribution of the two known RING domain functions to TRIM5α restriction of retrovirus infection.
authors: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors: Xing
authors: X
authors: Li
authors: Jonghwa
authors: J
authors: Kim
authors: Byeongwoon
authors: B
authors: Song
authors: Andrés
authors: A
authors: Finzi
authors: Beatriz
authors: B
authors: Pacheco
authors: Joseph
authors: J
authors: Sodroski
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002213:Capsid / Q000378:metabolism*; D002460:Cell Line; D004285:Dogs; D049452:Green Fluorescent Proteins / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D004860:Infectious Anemia Virus, Equine; D009052:Leukemia Virus, Murine; D008253:Macaca mulatta; D008856:Microscopy, Fluorescence; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012192:Retroviridae Infections / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D011506:Proteins; D049452:Green Fluorescent Proteins; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases
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