Open AccessCyclophilin A Levels Dictate Infection Efficiency of Human Immunodeficiency Virus Type 1 Capsid Escape Mutants A92E and G94D
Author(s) -
Laura M. J. Ylinen,
Torsten Schaller,
Amanda J. Price,
Adam J. Fletcher,
Mahdad Noursadeghi,
Leo C. James,
Greg J. Towers
Publication year - 2009
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.01876-08
Subject(s) - cypa , cyclophilin a , capsid , biology , infectivity , mutant , virology , cell culture , samhd1 , cis trans isomerases , virus , wild type , peptidylprolyl isomerase , microbiology and biotechnology , genetics , gene , rna , reverse transcriptase , isomerase
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.