Antiretroviral activity of ancestral TRIM5alpha.

Antiretroviral activity of ancestral TRIM5alpha. Research Abstract Details 

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Antiretroviral activity of ancestral TRIM5alpha. Abstract Text:

Valérie Goldschmidt,Angela Ciuffi,Millan Ortiz,David Brawand,Miguel Muñoz,Henrik Kaessmann,Amalio Telenti, Goldschmidt,Angela Ciuffi,Millan Ortiz,David Brawand,Miguel ,Henrik Kaessmann,Amalio Telenti,

The antiretroviral protein TRIM5alpha is known to have evolved different restriction capacities against various retroviruses, driven by positive Darwinian selection. However, how these different specificities have evolved in the primate lineages is not fully understood. Here we used ancestral protein resurrection to estimate the evolution of antiviral restriction specificities of TRIM5alpha on the primate lineage leading to humans. We used TRIM5alpha coding sequences from 24 primates for the reconstruction of ancestral TRIM5alpha sequences using maximum-likelihood and Bayesian approaches. Ancestral sequences were transduced into HeLa and CRFK cells. Stable cell lines were generated and used to test restriction of a panel of extant retroviruses (human immunodeficiency virus type 1 [HIV-1] and HIV-2, simian immunodeficiency virus [SIV] variants SIV(mac) and SIV(agm), and murine leukemia virus [MLV] variants N-MLV and B-MLV). The resurrected TRIM5alpha variant from the common ancestor of Old World primates (Old World monkeys and apes, approximately 25 million years before present) was effective against present day HIV-1. In contrast to the HIV-1 restriction pattern, we show that the restriction efficacy against other retroviruses, such as a murine oncoretrovirus (N-MLV), is higher for more recent resurrected hominoid variants. Ancestral TRIM5alpha variants have generally limited efficacy against HIV-2, SIV(agm), and SIV(mac). Our study sheds new light on the evolution of the intrinsic antiviral defense machinery and illustrates the utility of functional evolutionary reconstruction for characterizing recently emerged protein differences.

Antiretroviral activity of ancestral TRIM5alpha. Publishing Authors By Initials

V Goldschmidt,A Ciuffi,M Ortiz,D Brawand,M Muñoz,H Kaessmann,A Telenti,V Goldschmidt,A Ciuffi,M Ortiz,D Brawand,M ,H Kaessmann,A Telenti,

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Antiretroviral activity of ancestral TRIM5alpha. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of virology

VOLUME: 82

Page Numbers: 2089-96

Journal Abbreviation: J. Virol.

ISSN: 1098-5514

DAY: 12

MONTH: 12

YEAR: 2007

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LANGUAGE: eng

NlmUniqueID: 113724

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AFFILIATION: Institute of Microbiology, CHUV 1011 Lausanne, Switzerland.

Country: United States

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MEDLINETA: J Virol

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