PMID- 18586294 OWN - NLM STAT- MEDLINE DCOM- 20080923 LR - 20211203 IS - 1096-0341 (Electronic) IS - 0042-6822 (Print) IS - 0042-6822 (Linking) VI - 378 IP - 2 DP - 2008 Sep 1 TI - A human TRIM5alpha B30.2/SPRY domain mutant gains the ability to restrict and prematurely uncoat B-tropic murine leukemia virus. PG - 233-42 LID - 10.1016/j.virol.2008.05.008 [doi] AB - Human TRIM5alpha restricts N-tropic murine leukemia virus (N-MLV) but not B-tropic MLV (B-MLV) infection. Here we study B30.2/SPRY domain mutants of human TRIM5alpha that acquire the ability to inhibit B-MLV infection prior to reverse transcription without losing the ability to restrict N-MLV infection. Remarkably, these mutants gain the ability to decrease the amount of particulate B-MLV capsids in the cytosol of infected cells. In addition, these mutants gain the ability to restrict SIV(mac) and HIV-2 infection. B-MLV and SIV(mac) infections were blocked by the mutant TRIM5alpha proteins prior to reverse transcription. Thus, the range of retroviruses restricted by human TRIM5alpha can be increased by changes in the B30.2/SPRY domain, which also result in the ability to cause premature uncoating of the restricted retroviral capsid. FAU - Diaz-Griffero, Felipe AU - Diaz-Griffero F AD - Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA. FAU - Perron, Michel AU - Perron M FAU - McGee-Estrada, Kathleen AU - McGee-Estrada K FAU - Hanna, Robert AU - Hanna R FAU - Maillard, Pierre V AU - Maillard PV FAU - Trono, Didier AU - Trono D FAU - Sodroski, Joseph AU - Sodroski J LA - eng GR - R01 AI063987/AI/NIAID NIH HHS/United States GR - R01 AI063987-04/AI/NIAID NIH HHS/United States GR - AI60354/AI/NIAID NIH HHS/United States GR - AI063987/AI/NIAID NIH HHS/United States GR - R21 AI076094/AI/NIAID NIH HHS/United States GR - R21 AI076094-01/AI/NIAID NIH HHS/United States GR - P30 AI060354/AI/NIAID NIH HHS/United States GR - AI076094/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20080630 PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (Antiviral Restriction Factors) RN - 0 (Carrier Proteins) RN - 0 (Tripartite Motif Proteins) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 2.3.2.27 (TRIM5 protein, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - Antiviral Restriction Factors MH - Capsid/metabolism MH - Carrier Proteins/genetics/*physiology MH - Cell Line MH - Cytoplasm/virology MH - Genes, Reporter MH - Green Fluorescent Proteins/analysis/genetics MH - HIV-2/immunology MH - Humans MH - Leukemia Virus, Murine/*immunology/physiology MH - *Mutation, Missense MH - Protein Structure, Tertiary MH - Simian Immunodeficiency Virus/immunology MH - Tripartite Motif Proteins MH - Ubiquitin-Protein Ligases PMC - PMC2597210 MID - NIHMS67179 EDAT- 2008/07/01 09:00 MHDA- 2008/09/24 09:00 PMCR- 2009/09/01 CRDT- 2008/07/01 09:00 PHST- 2008/01/10 00:00 [received] PHST- 2008/01/31 00:00 [revised] PHST- 2008/05/05 00:00 [accepted] PHST- 2008/07/01 09:00 [pubmed] PHST- 2008/09/24 09:00 [medline] PHST- 2008/07/01 09:00 [entrez] PHST- 2009/09/01 00:00 [pmc-release] AID - S0042-6822(08)00310-3 [pii] AID - 10.1016/j.virol.2008.05.008 [doi] PST - ppublish SO - Virology. 2008 Sep 1;378(2):233-42. doi: 10.1016/j.virol.2008.05.008. Epub 2008 Jun 30.