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Journal of Virology, November 2004, p. 11816-11822, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11816-11822.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Influence of gag on Human Immunodeficiency Virus Type 1 Species-Specific Tropism

Yasuhiro Ikeda,{dagger} Laura M. J. Ylinen,{dagger} Maria Kahar-Bador, and Greg J. Towers*

Wohl Virion Centre and Department of Immunology and Molecular Pathology, Infection and Immunity, University College London, London, United Kingdom

Received 8 April 2004/ Accepted 16 June 2004

The narrow host range of human immunodeficiency virus type 1 (HIV-1) is due in part to dominant acting restriction factors in humans (Ref1) and monkeys (Lv1). Here we show that gag encodes determinants of species-specific lentiviral infection, related in part to such restriction factors. Interaction between capsid and host cyclophilin A (CypA) protects HIV-1 from restriction in human cells but is essential for maximal restriction in simian cells. We show that sequence variation between HIV-1 isolates leads to variation in sensitivity to restriction factors in human and simian cells. We present further evidence for the importance of target cell CypA over CypA packaged in virions, specifically in the context of gp160 pseudotyped HIV-1 vectors. We also show that sensitivity to restriction is controlled by an H87Q mutation in the capsid, implicated in the immune control of HIV-1, possibly linking immune and innate control of HIV-1 infection.

* Corresponding author. Mailing address: Wohl Virion Centre, Infection and Immunity, University College London, 46 Cleveland St., London W1T 4JF, United Kingdom. Phone: 44-20-7679-9535. Fax: 44-20-7679-9555. E-mail: g.towers{at}ucl.ac.uk.

{dagger} These authors contributed equally to this work.

Journal of Virology, November 2004, p. 11816-11822, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11816-11822.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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