Cyclophilin A levels dictate infection efficiency of human immunodeficiency virus type 1 capsid escape mutants A92E and G94D

Ylinen, L. M. J., Schaller, T., Price, A., Fletcher, A. J., Noursadeghi, M., James, L. C. and Towers, G. J. (2010) Cyclophilin A levels dictate infection efficiency of human immunodeficiency virus type 1 capsid escape mutants A92E and G94D. Journal of Virology, 83(4), pp. 2044-2047. (doi: 10.1128/jvi.01876-08) (PMID:19073742) (PMCID:PMC2643744)

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Abstract

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.

Item Type:Articles
Additional Information:This work was supported by Wellcome Trust fellowships to G.J.T. (WT076608) and M.N. (WT077161) and the Medical Research Council.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Fletcher, Dr Adam
Authors: Ylinen, L. M. J., Schaller, T., Price, A., Fletcher, A. J., Noursadeghi, M., James, L. C., and Towers, G. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Virology
Publisher:American Society for Microbiology
ISSN:0022-538X
ISSN (Online):1098-5514

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