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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.

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.
Published ahead of print on 10 December 2008.
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