Cyclophilin A levels dictate infection efficiency of human immunodeficiency virus type 1 capsid escape mutants A92E and G94D.
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.
Ylinen
Laura M J
LM
Medical Research Council Centre for Medical Molecular Virology, University College London, United Kingdom.
Schaller
Torsten
T
Price
Amanda
A
Fletcher
Adam J
AJ
Noursadeghi
Mahdad
M
James
Leo C
LC
Towers
Greg J
GJ
D036022:Capsid Proteins / Q000235:genetics* / Q000276:immunology*; D021984:Cyclophilin A / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D020125:Mutation, Missense
D036022:Capsid Proteins; D021984:Cyclophilin A