TRIM5 alpha Drives SIVsmm Evolution in Rhesus Macaques

The antagonistic interaction with host restriction proteins is a major driver of evolutionary change for viruses. We previously reported that polymorphisms of the TRIM5α B30.2/SPRY domain impacted the level of SIVsmm viremia in rhesus macaques. Viremia in macaques homozygous for the non-restrictive...

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Main Authors:	Wu, Fan, Kirmaier, Andrea, Goeken, Robert, Ourmanov, Ilnour, Hall, Laura, Morgan, Jennifer S., Matsuda, Kenta, Buckler-White, Alicia, Tomioka, Keiko, Plishka, Ronald, Whitted, Sonya, Johnson, Welkin, Hirsch, Vanessa M.
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749954/

id	pubmed-3749954
recordtype	oai_dc
spelling	pubmed-37499542013-08-29 TRIM5 alpha Drives SIVsmm Evolution in Rhesus Macaques Wu, Fan Kirmaier, Andrea Goeken, Robert Ourmanov, Ilnour Hall, Laura Morgan, Jennifer S. Matsuda, Kenta Buckler-White, Alicia Tomioka, Keiko Plishka, Ronald Whitted, Sonya Johnson, Welkin Hirsch, Vanessa M. Research Article The antagonistic interaction with host restriction proteins is a major driver of evolutionary change for viruses. We previously reported that polymorphisms of the TRIM5α B30.2/SPRY domain impacted the level of SIVsmm viremia in rhesus macaques. Viremia in macaques homozygous for the non-restrictive TRIM5α allele TRIM5Q was significantly higher than in macaques expressing two restrictive TRIM5alpha alleles TRIM5TFP/TFP or TRIM5Cyp/TFP. Using this model, we observed that despite an early impact on viremia, SIVsmm overcame TRIM5α restriction at later stages of infection and that increasing viremia was associated with specific amino acid substitutions in capsid. Two amino acid substitutions (P37S and R98S) in the capsid region were associated with escape from TRIM5TFP restriction and substitutions in the CypA binding-loop (GPLPA87-91) in capsid were associated with escape from TRIM5Cyp. Introduction of these mutations into the original SIVsmE543 clone not only resulted in escape from TRIM5α restriction in vitro but the P37S and R98S substitutions improved virus fitness in macaques with homozygous restrictive TRIMTFP alleles in vivo. Similar substitutions were observed in other SIVsmm strains following transmission and passage in macaques, collectively providing direct evidence that TRIM5α exerts selective pressure on the cross-species transmission of SIV in primates. Public Library of Science 2013-08-22 /pmc/articles/PMC3749954/ /pubmed/23990789 http://dx.doi.org/10.1371/journal.ppat.1003577 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wu, Fan Kirmaier, Andrea Goeken, Robert Ourmanov, Ilnour Hall, Laura Morgan, Jennifer S. Matsuda, Kenta Buckler-White, Alicia Tomioka, Keiko Plishka, Ronald Whitted, Sonya Johnson, Welkin Hirsch, Vanessa M.
spellingShingle	Wu, Fan Kirmaier, Andrea Goeken, Robert Ourmanov, Ilnour Hall, Laura Morgan, Jennifer S. Matsuda, Kenta Buckler-White, Alicia Tomioka, Keiko Plishka, Ronald Whitted, Sonya Johnson, Welkin Hirsch, Vanessa M. TRIM5 alpha Drives SIVsmm Evolution in Rhesus Macaques
author_facet	Wu, Fan Kirmaier, Andrea Goeken, Robert Ourmanov, Ilnour Hall, Laura Morgan, Jennifer S. Matsuda, Kenta Buckler-White, Alicia Tomioka, Keiko Plishka, Ronald Whitted, Sonya Johnson, Welkin Hirsch, Vanessa M.
author_sort	Wu, Fan
title	TRIM5 alpha Drives SIVsmm Evolution in Rhesus Macaques
title_short	TRIM5 alpha Drives SIVsmm Evolution in Rhesus Macaques
title_full	TRIM5 alpha Drives SIVsmm Evolution in Rhesus Macaques
title_fullStr	TRIM5 alpha Drives SIVsmm Evolution in Rhesus Macaques
title_full_unstemmed	TRIM5 alpha Drives SIVsmm Evolution in Rhesus Macaques
title_sort	trim5 alpha drives sivsmm evolution in rhesus macaques
description	The antagonistic interaction with host restriction proteins is a major driver of evolutionary change for viruses. We previously reported that polymorphisms of the TRIM5α B30.2/SPRY domain impacted the level of SIVsmm viremia in rhesus macaques. Viremia in macaques homozygous for the non-restrictive TRIM5α allele TRIM5Q was significantly higher than in macaques expressing two restrictive TRIM5alpha alleles TRIM5TFP/TFP or TRIM5Cyp/TFP. Using this model, we observed that despite an early impact on viremia, SIVsmm overcame TRIM5α restriction at later stages of infection and that increasing viremia was associated with specific amino acid substitutions in capsid. Two amino acid substitutions (P37S and R98S) in the capsid region were associated with escape from TRIM5TFP restriction and substitutions in the CypA binding-loop (GPLPA87-91) in capsid were associated with escape from TRIM5Cyp. Introduction of these mutations into the original SIVsmE543 clone not only resulted in escape from TRIM5α restriction in vitro but the P37S and R98S substitutions improved virus fitness in macaques with homozygous restrictive TRIMTFP alleles in vivo. Similar substitutions were observed in other SIVsmm strains following transmission and passage in macaques, collectively providing direct evidence that TRIM5α exerts selective pressure on the cross-species transmission of SIV in primates.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749954/
_version_	1612004904311717888

TRIM5 alpha Drives SIVsmm Evolution in Rhesus Macaques

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