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

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2008 Dec 17

PMID 19073742

Citations 46

Authors

Laura M J Ylinen

Torsten Schaller

Amanda Price

Adam J Fletcher

Mahdad Noursadeghi

Leo C James

Greg J Towers

Affiliations

Soon will be listed here.

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.

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