PMID- 15249685 OWN - NLM STAT- MEDLINE DCOM- 20040826 LR - 20240411 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 101 IP - 29 DP - 2004 Jul 20 TI - Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5alpha. PG - 10774-9 AB - Mammalian cells express several factors that act in a cell-autonomous manner to inhibit retrovirus replication. Among these are the Friend virus susceptibility factor 1/lentivirus susceptibility factor 1/restriction factor 1 (Ref1) class of restriction factors, which block infection by targeting the capsids of diverse retroviruses. Here we show that lentivirus susceptibility factor 1 and Ref1 are species-specific variants of tripartite interaction motif 5alpha (TRIM5alpha), a cytoplasmic body component recently shown to block HIV-1 infection in rhesus macaque cells, and can indeed block infection by widely divergent retroviruses. Depletion of TRIM5alpha from human cells relieved restriction of N-tropic murine leukemia virus (N-MLV), and expression of human TRIM5alpha in otherwise nonrestricting cells conferred specific resistance to N-MLV infection, indicating that TRIM5alpha is Ref1 or an essential component of Ref1. TRIM5alpha variants from humans, rhesus monkeys, and African green monkeys displayed different but overlapping restriction specificities that were quite accurately predicted by the restriction properties of the cells from which they were derived. All TRIM5alpha variants could inhibit infection by at least two different retroviruses, and African green monkey TRIM5alpha was able to inhibit infection by no less than four divergent retroviruses of human, non-human primate, equine, and murine origin. However, each TRIM5alpha variant was unable to restrict retroviruses isolated from the same species. These data indicate that TRIM5alpha can confer broad innate immunity to retrovirus infection in primate cells and is likely to be an important natural barrier to cross-species retrovirus transmission. FAU - Hatziioannou, Theodora AU - Hatziioannou T AD - Aaron Diamond AIDS Research Center, New York, NY 10016, USA. FAU - Perez-Caballero, David AU - Perez-Caballero D FAU - Yang, Annie AU - Yang A FAU - Cowan, Simone AU - Cowan S FAU - Bieniasz, Paul D AU - Bieniasz PD LA - eng SI - GENBANK/AY669399 GR - R01 AI050111/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20040712 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Antiviral Agents) RN - 0 (Antiviral Restriction Factors) RN - 0 (Carrier Proteins) RN - 0 (Protein Isoforms) 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 CIN - Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10496-7. PMID: 15252204 MH - Amino Acid Sequence MH - Animals MH - Antiviral Agents/genetics/*metabolism MH - Antiviral Restriction Factors MH - Carrier Proteins/chemistry/genetics/*metabolism MH - Cell Line MH - Humans MH - Macaca mulatta MH - Molecular Sequence Data MH - Protein Isoforms/genetics/metabolism MH - Retroviridae/*metabolism MH - Retroviridae Infections/metabolism MH - Sequence Alignment MH - Species Specificity MH - Tripartite Motif Proteins MH - Ubiquitin-Protein Ligases PMC - PMC490010 EDAT- 2004/07/14 05:00 MHDA- 2004/08/27 05:00 PMCR- 2005/01/20 CRDT- 2004/07/14 05:00 PHST- 2004/07/14 05:00 [pubmed] PHST- 2004/08/27 05:00 [medline] PHST- 2004/07/14 05:00 [entrez] PHST- 2005/01/20 00:00 [pmc-release] AID - 0402361101 [pii] AID - 10110774 [pii] AID - 10.1073/pnas.0402361101 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10774-9. doi: 10.1073/pnas.0402361101. Epub 2004 Jul 12.