PMID- 15994791 OWN - NLM STAT- MEDLINE DCOM- 20050721 LR - 20211203 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 79 IP - 14 DP - 2005 Jul TI - Human tripartite motif 5alpha domains responsible for retrovirus restriction activity and specificity. PG - 8969-78 AB - The tripartite motif 5alpha protein (TRIM5alpha) is one of several factors expressed by mammalian cells that inhibit retrovirus replication. Human TRIM5alpha (huTRIM5alpha) inhibits infection by N-tropic murine leukemia virus (N-MLV) but is inactive against human immunodeficiency virus type 1 (HIV-1). However, we show that replacement of a small segment in the carboxy-terminal B30.2/SPRY domain of huTRIM5alpha with its rhesus macaque counterpart (rhTRIM5alpha) endows it with the ability to potently inhibit HIV-1 infection. The B30.2/SPRY domain and an additional domain in huTRIM5alpha, comprising the amino-terminal RING and B-box components of the TRIM motif, are required for N-MLV restriction activity, while the intervening coiled-coil domain is necessary and sufficient for huTRIM5alpha multimerization. Truncated huTRIM5alpha proteins that lack either or both the N-terminal RING/B-Box or the C-terminal B30.2/SPRY domain form heteromultimers with full-length huTRIM5alpha and are dominant inhibitors of its N-MLV restricting activity, suggesting that homomultimerization of intact huTRIM5alpha monomers is necessary for N-MLV restriction. However, localization in large cytoplasmic bodies is not required for inhibition of N-MLV by huTRIM5alpha or for inhibition of HIV-1 by chimeric or rhTRIM5alpha. FAU - Perez-Caballero, David AU - Perez-Caballero D AD - Aaron Diamond AIDS Research Center, 455 First Ave., New York, NY 10021, USA. FAU - Hatziioannou, Theodora AU - Hatziioannou T FAU - Yang, Annie AU - Yang A FAU - Cowan, Simone AU - Cowan S FAU - Bieniasz, Paul D AU - Bieniasz PD LA - eng GR - R01 AI050111/AI/NIAID NIH HHS/United States GR - R01 AI064003/AI/NIAID NIH HHS/United States GR - R01AI050111/AI/NIAID NIH HHS/United States GR - R01AI64003/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Antiviral Agents) RN - 0 (Antiviral Restriction Factors) RN - 0 (Carrier Proteins) RN - 0 (Tripartite Motif Proteins) RN - EC 2.3.2.27 (TRIM5 protein, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - Amino Acid Sequence MH - Antiviral Agents/*physiology MH - Antiviral Restriction Factors MH - Carrier Proteins/*chemistry/*physiology MH - HIV-1/physiology MH - HeLa Cells MH - Humans MH - Leukemia Virus, Murine/physiology MH - Molecular Sequence Data MH - Retroviridae Infections/*prevention & control MH - Structure-Activity Relationship MH - Tripartite Motif Proteins MH - Ubiquitin-Protein Ligases PMC - PMC1168745 EDAT- 2005/07/05 09:00 MHDA- 2005/07/22 09:00 PMCR- 2005/07/01 CRDT- 2005/07/05 09:00 PHST- 2005/07/05 09:00 [pubmed] PHST- 2005/07/22 09:00 [medline] PHST- 2005/07/05 09:00 [entrez] PHST- 2005/07/01 00:00 [pmc-release] AID - 79/14/8969 [pii] AID - 0255-05 [pii] AID - 10.1128/JVI.79.14.8969-8978.2005 [doi] PST - ppublish SO - J Virol. 2005 Jul;79(14):8969-78. doi: 10.1128/JVI.79.14.8969-8978.2005.