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Journal of Virology, February 2009, p. 2044-2047, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.01876-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cyclophilin A Levels Dictate Infection Efficiency of Human Immunodeficiency Virus Type 1 Capsid Escape Mutants A92E and G94D {triangledown}

Laura M. J. Ylinen,1 Torsten Schaller,1 Amanda Price,2 Adam J. Fletcher,1 Mahdad Noursadeghi,1 Leo C. James,2 and Greg J. Towers1*

Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T4JF, United Kingdom,1 Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, United Kingdom2

Received 5 September 2008/ Accepted 27 November 2008

Cyclophilin A (CypA) is an important human immunodeficiency virus type 1 (HIV-1) cofactor in human cells. HIV-1 A92E and G94D capsid escape mutants arise during CypA inhibition and in certain cell lines are dependent on CypA inhibition. Here we show that dependence on CypA inhibition is due to high CypA levels. Restricted HIV-1 is stable, and remarkably, restriction is augmented by arresting cell division. Nuclear entry is not inhibited. We propose that high CypA levels and capsid mutations combine to disturb uncoating, leading to poor infectivity, particularly in arrested cells. Our data suggest a role for CypA in uncoating the core of HIV-1 to facilitate integration.


* Corresponding author. Mailing address: Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T4JF, United Kingdom. Phone: 44-20 7679 9535. Fax: 44-20 7679 9545. E-mail: g.towers{at}ucl.ac.uk

{triangledown} Published ahead of print on 10 December 2008.


Journal of Virology, February 2009, p. 2044-2047, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.01876-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




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