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Journal of Virology, September 2005, p. 11580-11587, Vol. 79, No. 18
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.18.11580-11587.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Differential Restriction of Human Immunodeficiency Virus Type 2 and Simian Immunodeficiency Virus SIVmac by TRIM5{alpha} Alleles

Laura M. J. Ylinen, Zuzana Keckesova, Sam J. Wilson, Srinika Ranasinghe,{dagger} and Greg J. Towers*

Wohl Virion Center, Division of Infection and Immunity, University College London, London, United Kingdom

Received 1 April 2005/ Accepted 1 July 2005

Primate lentiviruses have narrow host ranges, due in part to their sensitivities to mammalian intracellular antiviral factors such as APOBEC3G and TRIM5{alpha}. Despite the protection provided by this innate immune system, retroviruses are able to transfer between species where they can cause disease. This is true for sooty mangabey simian immunodeficiency virus, which has transferred to humans as HIV-2 and to rhesus macaques as SIVmac, where it causes AIDS. Here we examine the sensitivities of the closely related HIV-2 and SIVmac to restriction by TRIM5{alpha}. We show that rhesus TRIM5{alpha} can restrict HIV-2 but not the closely related SIVmac. SIVmac has not completely escaped TRIM5{alpha}, as shown by its sensitivity to distantly related TRIM5{alpha} from the New World squirrel monkey. Squirrel monkey TRIM5{alpha} blocks SIVmac infection after DNA synthesis and is not saturable with restriction-sensitive virus-like particles. We map the determinant for TRIM5{alpha} sensitivity to the structure in the capsid protein that recruits CypA into HIV-1 virions. We also make an SIV, mutated at this site, which bypasses restriction in all cells tested.

* Corresponding author. Mailing address: Wohl Virion Center, Windeyer Building, University College London, 46 Cleveland St., London W1T4JF, United Kingdom. Phone: 44 020 7679 9535. Fax: 44 020 7679 9555. E-mail: g.towers{at}ucl.ac.uk.

{dagger} Present address: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.

Journal of Virology, September 2005, p. 11580-11587, Vol. 79, No. 18
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.18.11580-11587.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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