The Hypervariable HIV-1 Capsid Protein Residues Comprise HLA-Driven CD8+ T-Cell Escape Mutations and Covarying HLA-Independent Polymorphisms

被引：22

作者：

Crawford, Hayley ^{[1
,2
]}

Matthews, Philippa C. ^{[1
]}

Schaefer, Malinda ^{[3
]}

Carlson, Jonathan M. ^{[4
]}

Leslie, Alasdair ^{[2
]}

Kilembe, William ^{[5
]}

Allen, Susan ^{[5
,6
]}

Ndung'u, Thumbi ^{[7
]}

Heckerman, David ^{[4
]}

Hunter, Eric ^{[3
,5
]}

Goulder, Philip J. R. ^{[1
,7
]}

机构：

[1] Univ Oxford, Dept Paediat, Oxford OX1 3SY, England

[2] Univ Oxford, Weatherall Inst Mol Med, Oxford OX3 9DS, England

[3] Emory Univ, Emory Vaccine Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA

[4] Microsoft Res, Los Angeles, CA 90024 USA

[5] Zambia Emory HIV Res Project ZEHRP, Lusaka, Zambia

[6] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30329 USA

[7] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa

来源：

JOURNAL OF VIROLOGY | 2011年 / 85卷 / 03期

基金：

美国国家卫生研究院; 英国惠康基金;

关键词：

HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1; SUBTYPE-C; REPLICATION CAPACITY; COMPENSATORY MUTATION; LYMPHOCYTE RESPONSE; VIRAL CONTROL; GAG PROTEIN; INFECTION; VIREMIA; TRANSMISSION;

D O I：

10.1128/JVI.01879-10

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

One proposed HIV vaccine strategy is to induce Gag-specific CD8(+) T-cell responses that can corner the virus, through fitness cost of viral escape and unavailability of compensatory mutations. We show here that the most variable capsid residues principally comprise escape mutants driven by protective alleles HLA-B*57, -5801, and -8101 and covarying HLA-independent polymorphisms that arise in conjunction with these escape mutations. These covarying polymorphisms are potentially compensatory and are concentrated around three tropism-determining loops of p24, suggesting structural interdependencies. Our results demonstrate complex patterns of adaptation of HIV under immune selection pressure, the understanding of which should aid vaccine design.

引用

页码：1384 / 1390

页数：7

共 37 条

[1] Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes [J].

Barouch, DH ;

Kunstman, J ;

Kuroda, MJ ;

Schmitz, JE ;

Santra, S ;

Peyerl, FW ;

Krivulka, GR ;

Beaudry, K ;

Lifton, MA ;

Gorgone, DA ;

Montefiori, DC ;

Lewis, MG ;

Wolinsky, SM ;

Letvin, NL .

NATURE, 2002, 415 (6869) :335-339

[2] Covariability of V3 loop amino acids [J].

Bickel, PJ ;

Cosman, PC ;

Olshen, RA ;

Spector, PC ;

Rodrigo, AG ;

Mullins, JI .

AIDS RESEARCH AND HUMAN RETROVIRUSES, 1996, 12 (15) :1401-1411

[3] VIRUS-SPECIFIC CD8+ CYTOTOXIC T-LYMPHOCYTE ACTIVITY ASSOCIATED WITH CONTROL OF VIREMIA IN PRIMARY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION [J].

BORROW, P ;

LEWICKI, H ;

HAHN, BH ;

SHAW, GM ;

OLDSTONE, MBA .

JOURNAL OF VIROLOGY, 1994, 68 (09) :6103-6110

[4] Reduced Viral Replication Capacity of Human Immunodeficiency Virus Type 1 Subtype C Caused by Cytotoxic-T-Lymphocyte Escape Mutations in HLA-B57 Epitopes of Capsid Protein [J].

Boutwell, Christian L. ;

Rowley, Christopher F. ;

Essex, M. .

JOURNAL OF VIROLOGY, 2009, 83 (06) :2460-2468

[5] Use of a novel GFP reporter cell line to examine replication capacity of CXCR4- and CCR5-tropic HIV-1 by flow cytometry [J].

Brockman, MA ;

Tanzi, GO ;

Walker, BD ;

Allen, TM .

JOURNAL OF VIROLOGICAL METHODS, 2006, 131 (02) :134-142

[6] Escape and compensation from early HLA-B57-Mediated cytotoxic T-lymphocyte pressure on human immunodeficiency virus type 1 Gag alter capsid interactions with cyclophilin A [J].

Brockman, Mark A. ;

Schneidewind, Arne ;

Lahaie, Matthew ;

Schmidt, Aaron ;

Miura, Toshiyuki ;

DeSouza, Ivna ;

Ryvkin, Faina ;

Derdeyn, Cynthia A. ;

Allen, Susan ;

Hunter, Eric ;

Mulenga, Joseph ;

Goepfert, Paul A. ;

Walker, Bruce D. ;

Allen, Todd M. .

JOURNAL OF VIROLOGY, 2007, 81 (22) :12608-12618

[7] Phototyping: Comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP) [J].

Bunce, M ;

ONeill, CM ;

Barnardo, MCNM ;

Krausa, P ;

Browning, MJ ;

Morris, PJ ;

Welsh, KI .

TISSUE ANTIGENS, 1995, 46 (05) :355-367

[8] Phylogenetic Dependency Networks: Inferring Patterns of CTL Escape and Codon Covariation in HIV-1 Gag [J].

Carlson, Jonathan M. ;

Brumme, Zabrina L. ;

Rousseau, Christine M. ;

Brumme, Chanson J. ;

Matthews, Philippa ;

Kadie, Carl ;

Mullins, James I. ;

Walker, Bruce D. ;

Harrigan, P. Richard ;

Goulder, Philip J. R. ;

Heckerman, David .

PLOS COMPUTATIONAL BIOLOGY, 2008, 4 (11)

[9] Compensatory mutation partially restores fitness and delays reversion of escpe mutation within the immunodominant HLA-B*5703-restricted Gag epitope in chronic human immunodeficiency virus type 1 infection [J].

Crawford, Hayley ;

Prado, Julia G. ;

Leslie, Alasdair ;

Hue, Stephane ;

Honeyborne, Isobella ;

Reddy, Sharon ;

van der Stok, Mary ;

Mncube, Zenele ;

Brander, Christian ;

Rousseau, Christine ;

Mullins, James I. ;

Kaslow, Richard ;

Goepfert, Paul ;

Allen, Susan ;

Hunter, Eric ;

Mulenga, Joseph ;

Kiepiela, Photini ;

Walker, Bruce D. ;

Goulder, Philip J. R. .

JOURNAL OF VIROLOGY, 2007, 81 (15) :8346-8351

[10] Evolution of HLA-B*5703 HIV-1 escape mutations in HLA-B*5703-positive individuals and their transmission recipients [J].

Crawford, Hayley ;

Lumm, Wendy ;

Leslie, Alasdair ;

Schaefer, Malinda ;

Boeras, Debrah ;

Prado, Julia G. ;

Tang, Jianming ;

Farmer, Paul ;

Ndung'u, Thumbi ;

Lakhi, Shabir ;

Gilmour, Jill ;

Goepfert, Paul ;

Walker, Bruce D. ;

Kaslow, Richard ;

Mulenga, Joseph ;

Allen, Susan ;

Goulder, Philip J. R. ;

Hunter, Eric .

JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (04) :909-921

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