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

被引：57

作者：

Ylinen, Laura M. J. ^{[1
]}

Schaller, Torsten ^{[1
]}

Price, Amanda ^{[2
]}

Fletcher, Adam J. ^{[1
]}

Noursadeghi, Mahdad ^{[1
]}

James, Leo C. ^{[2
]}

Towers, Greg J. ^{[1
]}

机构：

[1] UCL, Div Infect & Immun, Ctr Med Mol Virol, MRC, London W1T 4JF, England

[2] MRC, Mol Biol Lab, Cambridge CB2 0QH, England

来源：

JOURNAL OF VIROLOGY | 2009年 / 83卷 / 04期

基金：

英国惠康基金;

关键词：

OLD-WORLD MONKEY; RESTRICTION FACTORS; HOST RESTRICTION; HIV-1; VIRIONS; HUMAN-CELLS; GAG; REPLICATION; CATALYSIS; PROTEIN; TARGET;

D O I：

10.1128/JVI.01876-08

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：2044 / 2047

页数：4

共 23 条

[1] Spontaneous mutations in the human immunodeficiency virus type 1 gag gene that affect viral replication in the presence of cyclosporins [J].

Aberham, C ;

Weber, S ;

Phares, W .

JOURNAL OF VIROLOGY, 1996, 70 (06) :3536-3544

[2] Cyclophilin A is required for TRIM5α-mediated resistance to HIV-1 in old world monkey cells [J].

Berthoux, L ;

Sebastian, S ;

Sokolskaja, E ;

Luban, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (41) :14849-14853

[3] Catalysis and binding of cyclophilin a with different HIV-1 capsid constructs [J].

Bosco, DA ;

Kern, D .

BIOCHEMISTRY, 2004, 43 (20) :6110-6119

[4] Catalysis of cis/trans isomerization in native HIV-1 capsid by human cyclophilin A [J].

Bosco, DA ;

Eisenmesser, EZ ;

Pochapsky, S ;

Sundquist, WI ;

Kern, D .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (08) :5247-5252

[5] Cyclosporine A-resistant human immunodeficiency virus type 1 mutants demonstrate that Gag encodes the functional target of cyclophilin A [J].

Braaten, D ;

Aberham, C ;

Franke, EK ;

Yin, L ;

Phares, W ;

Luban, J .

JOURNAL OF VIROLOGY, 1996, 70 (08) :5170-5176

[6] A quantitative assay for HIV DNA integration in vivo [J].

Butler, SL ;

Hansen, MST ;

Bushman, FD .

NATURE MEDICINE, 2001, 7 (05) :631-634

[7] Structural requirements for recognition of the human immunodeficiency virus type 1 core during host restriction in owl monkey cells [J].

Forshey, BM ;

Shi, J ;

Aiken, C .

JOURNAL OF VIROLOGY, 2005, 79 (02) :869-875

[8] SPECIFIC INCORPORATION OF CYCLOPHILIN-A INTO HIV-1 VIRIONS [J].

FRANKE, EK ;

YUAN, HEH ;

LUBAN, J .

NATURE, 1994, 372 (6504) :359-362

[9] FORMATION AND STRUCTURE OF INFECTIOUS DNA OF SPLEEN NECROSIS VIRUS [J].

FRITSCH, E ;

TEMIN, HM .

JOURNAL OF VIROLOGY, 1977, 21 (01) :119-130

[10] Cyclophilin interactions with incoming human immunodeficiency virus type 1 capsids with opposing effects on infectivity in human cells [J].

Hatziioannou, T ;

Perez-Caballero, D ;

Cowan, S ;

Bieniasz, PD .

JOURNAL OF VIROLOGY, 2005, 79 (01) :176-183

← 1 2 3 →