PMID- 21345948 OWN - NLM STAT- MEDLINE DCOM- 20110614 LR - 20220129 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 85 IP - 9 DP - 2011 May TI - Unique spectrum of activity of prosimian TRIM5alpha against exogenous and endogenous retroviruses. PG - 4173-83 LID - 10.1128/JVI.00075-11 [doi] AB - Lentiviruses, the genus of retrovirus that includes HIV-1, rarely endogenize. Some lemurs uniquely possess an endogenous lentivirus called PSIV ("prosimian immunodeficiency virus"). Thus, lemurs provide the opportunity to study the activity of host defense factors, such as TRIM5alpha, in the setting of germ line invasion. We characterized the activities of TRIM5alpha proteins from two distant lemurs against exogenous retroviruses and a chimeric PSIV. TRIM5alpha from gray mouse lemur, which carries PSIV in its genome, exhibited the narrowest restriction activity. One allelic variant of gray mouse lemur TRIM5alpha restricted only N-tropic murine leukemia virus (N-MLV), while a second variant restricted N-MLV and, uniquely, B-tropic MLV (B-MLV); both variants poorly blocked PSIV. In contrast, TRIM5alpha from ring-tailed lemur, which does not contain PSIV in its genome, revealed one of the broadest antiviral activities reported to date against lentiviruses, including PSIV. Investigation into the antiviral specificity of ring-tailed lemur TRIM5alpha demonstrated a major contribution of a 32-amino-acid expansion in variable region 2 (v2) of the B30.2/SPRY domain to the breadth of restriction. Data on lemur TRIM5alpha and the prediction of ancestral simian sequences hint at an evolutionary scenario where antiretroviral specificity is prominently defined by the lineage-specific expansion of the variable loops of B30.2/SPRY. FAU - Rahm, Nadia AU - Rahm N AD - Institute of Microbiology, University Hospital Center and University of Lausanne, CHUV 1011 Lausanne, Switzerland. FAU - Yap, Melvyn AU - Yap M FAU - Snoeck, Joke AU - Snoeck J FAU - Zoete, Vincent AU - Zoete V FAU - Munoz, Miguel AU - Munoz M FAU - Radespiel, Ute AU - Radespiel U FAU - Zimmermann, Elke AU - Zimmermann E FAU - Michielin, Olivier AU - Michielin O FAU - Stoye, Jonathan P AU - Stoye JP FAU - Ciuffi, Angela AU - Ciuffi A FAU - Telenti, Amalio AU - Telenti A LA - eng GR - MC_U117512710/MRC_/Medical Research Council/United Kingdom GR - P41 RR001081/RR/NCRR NIH HHS/United States GR - U117512710/MRC_/Medical Research Council/United Kingdom GR - P41 RR-01081/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110223 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Carrier Proteins) SB - IM MH - Amino Acid Sequence MH - Animals MH - Carrier Proteins/chemistry/genetics/*metabolism MH - Cluster Analysis MH - Evolution, Molecular MH - Lemur/*immunology MH - Models, Molecular MH - Molecular Sequence Data MH - Phylogeny MH - Protein Structure, Tertiary MH - Retroviridae/*immunology MH - Sequence Homology, Amino Acid PMC - PMC3126249 EDAT- 2011/02/25 06:00 MHDA- 2011/06/15 06:00 PMCR- 2011/11/01 CRDT- 2011/02/25 06:00 PHST- 2011/02/25 06:00 [entrez] PHST- 2011/02/25 06:00 [pubmed] PHST- 2011/06/15 06:00 [medline] PHST- 2011/11/01 00:00 [pmc-release] AID - JVI.00075-11 [pii] AID - 0075-11 [pii] AID - 10.1128/JVI.00075-11 [doi] PST - ppublish SO - J Virol. 2011 May;85(9):4173-83. doi: 10.1128/JVI.00075-11. Epub 2011 Feb 23.