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Journal of Virology, March 2008, p. 2089-2096, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.01828-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Antiretroviral Activity of Ancestral TRIM5{alpha}{triangledown}

Valérie Goldschmidt,1,{dagger} Angela Ciuffi,1,{dagger} Millan Ortiz,1 David Brawand,2 Miguel Muñoz,1 Henrik Kaessmann,2* and Amalio Telenti1*

Institute of Microbiology, University Hospital, 1011 Lausanne,1 Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland2

Received 20 August 2007/ Accepted 27 November 2007

The antiretroviral protein TRIM5{alpha} 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 TRIM5{alpha} on the primate lineage leading to humans. We used TRIM5{alpha} coding sequences from 24 primates for the reconstruction of ancestral TRIM5{alpha} 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 SIVmac and SIVagm, and murine leukemia virus [MLV] variants N-MLV and B-MLV). The resurrected TRIM5{alpha} variant from the common ancestor of Old World primates (Old World monkeys and apes, ~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 TRIM5{alpha} variants have generally limited efficacy against HIV-2, SIVagm, and SIVmac. 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.

* Corresponding authors. Mailing address for A. Telenti: Institute of Microbiology, CHUV 1011 Lausanne, Switzerland. Phone: 41 21 314 05 50. Fax: 41 21 314 40 95. E-mail: amalio.telenti{at}chuv.ch. Mailing address for H. Kaessmann: University of Lausanne, Bâtiment Génopode, 1015 Lausanne, Switzerland. Phone: 41 21 692 39 07. Fax: 41 21 692 39 65. E-mail: Henrik.Kaessmann{at}unil.ch

{triangledown} Published ahead of print on 12 December 2007.

{dagger} V.G. and A.C. contributed equally to this study.

Journal of Virology, March 2008, p. 2089-2096, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.01828-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ortiz, M., Guex, N., Patin, E., Martin, O., Xenarios, I., Ciuffi, A., Quintana-Murci, L., Telenti, A. (2009). Evolutionary Trajectories of Primate Genes Involved in HIV Pathogenesis. Mol Biol Evol 26: 2865-2875 [Abstract] [Full Text]  


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