Antiretroviral activity of ancestral TRIM5alpha.

Details

Serval ID
serval:BIB_62DC7EF469B4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Antiretroviral activity of ancestral TRIM5alpha.
Journal
Journal of Virology
Author(s)
Goldschmidt V., Ciuffi A., Ortiz M., Brawand D., Muñoz M., Kaessmann H., Telenti A.
ISSN
1098-5514[electronic], 0022-538X[linking]
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
82
Number
5
Pages
2089-2096
Language
english
Abstract
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.
Keywords
Animals, Evolution, Molecular, Hela Cells, Humans, Mutagenesis, Site-Directed, Primates, Proteins/genetics, Proteins/physiology, Retroviridae/pathogenicity
Pubmed
Web of science
Open Access
Yes
Create date
22/02/2008 15:45
Last modification date
20/08/2019 15:19
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