Tetherin antagonism by Vpu protects HIV-infected cells from antibody-dependent cell-mediated cytotoxicity

被引：131

作者：

Arias, Juan F. ^{[1
]}

Heyer, Lisa N. ^{[1
]}

von Bredow, Benjamin ^{[1
]}

Weisgrau, Kim L. ^{[2
]}

Moldt, Brian ^{[3
,4
]}

Burton, Dennis R. ^{[3
,4
,5
,6
]}

Rakasz, Eva G. ^{[2
]}

Evans, David T. ^{[1
]}

机构：

[1] Harvard Univ, New England Primate Res Ctr, Sch Med, Dept Microbiol & Immunobiol, Southborough, MA 01772 USA

[2] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA

[3] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[4] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA

[5] MIT, Ragon Inst MGH, Cambridge, MA 02139 USA

[6] Harvard Univ, Cambridge, MA 02139 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 17期

关键词：

BST-2; CD317; AIDS; lentivirus; IMMUNODEFICIENCY-VIRUS TYPE-1; IN-VITRO; MEMBRANE-PROTEIN; DOWN-REGULATION; INHIBITS HIV-1; RESTRICTION; RELEASE; DEGRADATION; MECHANISM; ASSAY;

D O I：

10.1073/pnas.1321507111

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Tetherin is an IFN-inducible transmembrane protein that inhibits the detachment of enveloped viruses from infected cells. HIV-1 overcomes this restriction factor by expressing HIV-1 viral protein U (Vpu), which down-regulates and degrades tetherin. We report that mutations in Vpu that impair tetherin antagonism increase the susceptibility of HIV-infected cells to antibody-dependent cellmediated cytotoxicity (ADCC), and conversely that RNAi knockdown of tetherin, but not other cellular proteins down-modulated by Vpu, decreases the susceptibility of HIV-infected cells to ADCC. These results reveal that Vpu protects HIV-infected cells from ADCC as a function of its ability to counteract tetherin. By serving as link between innate and adaptive immunity, the antiviral activity of tetherin may be augmented by virus-specific antibodies, and hence much greater than previously appreciated.

引用

页码：6425 / 6430

页数：6

共 53 条

[1] PRODUCTION OF ACQUIRED IMMUNODEFICIENCY SYNDROME-ASSOCIATED RETROVIRUS IN HUMAN AND NONHUMAN CELLS TRANSFECTED WITH AN INFECTIOUS MOLECULAR CLONE [J].

ADACHI, A ;

GENDELMAN, HE ;

KOENIG, S ;

FOLKS, T ;

WILLEY, R ;

RABSON, A ;

MARTIN, MA .

JOURNAL OF VIROLOGY, 1986, 59 (02) :284-291

[2] ADCC Develops Over Time during Persistent Infection with Live-Attenuated SIV and Is Associated with Complete Protection against SIVmac251 Challenge [J].

Alpert, Michael D. ;

Harvey, Jackson D. ;

Lauer, W. Anderson ;

Reeves, R. Keith ;

Piatak, Michael, Jr. ;

Carville, Angela ;

Mansfield, Keith G. ;

Lifson, Jeffrey D. ;

Li, Wenjun ;

Desrosiers, Ronald C. ;

Johnson, R. Paul ;

Evans, David T. .

PLOS PATHOGENS, 2012, 8 (08)

[3] A Novel Assay for Antibody-Dependent Cell-Mediated Cytotoxicity against HIV-1-or SIV-Infected Cells Reveals Incomplete Overlap with Antibodies Measured by Neutralization and Binding Assays [J].

Alpert, Michael D. ;

Heyer, Lisa N. ;

Williams, David E. J. ;

Harvey, Jackson D. ;

Greenough, Thomas ;

Allhorn, Maria ;

Evans, David T. .

JOURNAL OF VIROLOGY, 2012, 86 (22) :12039-12052

[4] HIV evolution in response to HLA-restricted CTL selection pressures: a population-based perspective [J].

Carlson, Jonathan M. ;

Brumme, Zabrina L. .

MICROBES AND INFECTION, 2008, 10 (05) :455-461

[5] HIV-1 infects multipotent progenitor cells causing cell death and establishing latent cellular reservoirs [J].

Carter, Christoph C. ;

Onafuwa-Nuga, Adewunmi ;

McNamara, Lucy A. ;

Riddell, James ;

Bixby, Dale ;

Savona, Michael R. ;

Collins, Kathleen L. .

NATURE MEDICINE, 2010, 16 (04) :446-U127

[6] Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure [J].

Chung, Amy W. ;

Isitman, Gamze ;

Navis, Marjon ;

Kramski, Marit ;

Center, Rob J. ;

Kent, Stephen J. ;

Stratov, Ivan .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (18) :7505-7510

[7] Identification of Alternatively Translated Tetherin Isoforms with Differing Antiviral and Signaling Activities [J].

Cocka, Luis J. ;

Bates, Paul .

PLOS PATHOGENS, 2012, 8 (09)

[8] Vpu Directs the Degradation of the Human Immunodeficiency Virus Restriction Factor BST-2/Tetherin via a βTrCP-Dependent Mechanism [J].

Douglas, Janet L. ;

Viswanathan, Kasinath ;

McCarroll, Matthew N. ;

Gustin, Jean K. ;

Frueh, Klaus ;

Moses, Ashlee V. .

JOURNAL OF VIROLOGY, 2009, 83 (16) :7931-7947

[9] BST-2/tetherin: a new component of the innate immune response to enveloped viruses [J].

Evans, David T. ;

Serra-Moreno, Ruth ;

Singh, Rajendra K. ;

Guatelli, John C. .

TRENDS IN MICROBIOLOGY, 2010, 18 (09) :388-396

[10] Direct Restriction of Virus Release and Incorporation of the Interferon-Induced Protein BST-2 into HIV-1 Particles [J].

Fitzpatrick, Kathleen ;

Skasko, Mark ;

Deerinck, Thomas J. ;

Crum, John ;

Ellisman, Mark H. ;

Guatelli, John .

PLOS PATHOGENS, 2010, 6 (03)

← 1 2 3 4 5 6 →