HIV-1 Antagonism of CD317 Is Species Specific and Involves Vpu-Mediated Proteasomal Degradation of the Restriction Factor

被引：230

作者：

Goffinet, Christine ^{[1
]}

Allespach, Ina ^{[1
]}

Homann, Stefanie ^{[1
]}

Tervo, Hanna-Mari ^{[1
]}

Habermann, Anja ^{[1
]}

Rupp, Daniel ^{[1
]}

Oberbremer, Lena ^{[1
]}

Kern, Christian ^{[1
]}

Tibroni, Nadine ^{[1
]}

Welsch, Sonja ^{[1
,2
,3
]}

Krijnse-Locker, Jacomine ^{[1
,2
]}

Banting, George ^{[4
]}

Kraeusslich, Hans-Georg ^{[1
]}

Fackler, Oliver T. ^{[1
]}

Keppler, Oliver T. ^{[1
]}

机构：

[1] Heidelberg Univ, Dept Virol, Heidelberg, Germany

[2] Cell Biol & Biophys Program, EMBL, Heidelberg, Germany

[3] Univ Oxford, Wellcome Trust Ctr Human Genet, Div Struct Biol, Oxford OX3 7BN, England

[4] Univ Bristol, Dept Biochem, Bristol BS8 1TD, Avon, England

来源：

CELL HOST & MICROBE | 2009年 / 5卷 / 03期

关键词：

PARTICLE RELEASE; CELL-SURFACE; INHIBITS HIV-1; VIRUS; PROTEIN; GLYCOPROTEIN; VIF; ENHANCEMENT; MATURATION; INFECTION;

D O I：

10.1016/j.chom.2009.01.009

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Mammals encode proteins that inhibit viral replication at the cellular level. In turn, certain viruses have evolved genes that can functionally counteract these intrinsic restrictions. Human CD317 (BST-2/HM1.24/tetherin) is a restriction factor that blocks release of human immunodeficiency virus type 1 (HIV-1) from the cell surface and can be overcome by HIV-1 Vpu. Here, we show that mouse and rat CD317 potently inhibit HIV-1 release but are resistant to Vpu. Inter-species chimeras reveal that the rodent-specific resistance and human-specific sensitivity to Vpu antagonism involve all three major structural domains of CD317. To promote virus release, Vpu depletes cellular pools of human CD317, but not of the rodent orthologs, by accelerating its degradation via the 20S proteasome. Thus, HIV-1 Vpu suppresses the expression of the CD317 antiviral factor in human cells, and the species-specific resistance to this suppression may guide the development of small animal models of HIV infection.

引用

页码：285 / 297

页数：13

共 47 条

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