HIV-1 Vpu Mediates HLA-C Downregulation

被引：110

作者：

Apps, Richard ^{[1
]}

Del Prete, Gregory Q. ^{[2
]}

Chatterjee, Pramita ^{[1
]}

Lara, Abigail ^{[2
]}

Brumme, Zabrina L. ^{[3
,4
]}

Brockman, Mark A. ^{[3
,4
]}

Neil, Stuart ^{[5
]}

Pickering, Suzanne ^{[5
]}

Schneider, Douglas K. ^{[2
]}

Piechocka-Trocha, Alicja ^{[6
,7
]}

Walker, Bruce D. ^{[6
,7
]}

Thomas, Rasmi ^{[8
]}

Shaw, George M. ^{[9
,10
]}

Hahn, Beatrice H. ^{[9
,10
]}

Keele, Brandon F. ^{[2
]}

Lifson, Jeffrey D. ^{[2
]}

Carrington, Mary ^{[1
,6
,7
]}

机构：

[1] Frederick Natl Lab, Canc & Inflammat Program, Leidos Biomed Res, Frederick, MD 21702 USA

[2] Frederick Natl Lab, AIDS & Canc Virus Program, Leidos Biomed Res, Frederick, MD 21702 USA

[3] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada

[4] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC V67 1Y6, Canada

[5] Guys Hosp, Kings Coll London, Sch Med, Dept Infect Dis, London SE1 9RT, England

[6] MIT, Massachusetts Gen Hosp, Ragon Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[7] Harvard Univ, Cambridge, MA 02139 USA

[8] US Mil HIV Res Program, Host Genet Sect, Silver Spring, MD 20910 USA

[9] Univ Penn, Dept Med, Philadelphia, PA 19104 USA

[10] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA

来源：

CELL HOST & MICROBE | 2016年 / 19卷 / 05期

关键词：

CLASS-I MOLECULES; IMMUNODEFICIENCY-VIRUS TYPE-1; COMPLEX CLASS-I; NATURAL-KILLER-CELLS; MONOCLONAL-ANTIBODIES; EXPRESSION LEVELS; INFECTED CELLS; T-LYMPHOCYTES; NEF PROTEIN; CLONES;

D O I：

10.1016/j.chom.2016.04.005

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Many pathogens evade cytotoxic T lymphocytes (CTLs) by downregulating HLA molecules on infected cells, but the loss of HLA can trigger NK cell-mediated lysis. HIV-1 is thought to subvert CTLs while preserving NK cell inhibition by Nef-mediated downregulation of HLA-A and -B but not HLA-C molecules. We find that HLA-C is downregulated by most primary HIV-1 clones, including transmitted founder viruses, in contrast to the laboratory-adapted NL4-3 virus. HLA-C reduction ismediated by viral Vpu and reduces the ability of HLA-C restricted CTLs to suppress viral replication in CD4+ cells in vitro. HLA-A/B are unaffected by Vpu, and primary HIV-1 clones vary in their ability to downregulate HLA-C, possibly in response to whether CTLs or NK cells dominate immune pressure through HLA-C. HIV-2 also suppresses HLA-C expression through distinct mechanisms, underscoring the immune pressure HLA-C exerts on HIV. This viral immune evasion casts new light on the roles of CTLs and NK cells in immune responses against HIV.

引用

页码：686 / 695

页数：10

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