HIV-1 targets L-selectin for adhesion and induces its shedding for viral release

被引:15
作者
Kononchik, Joseph [1 ]
Ireland, Joanna [1 ]
Zou, Zhongcheng [1 ]
Segura, Jason [1 ]
Holzapfel, Genevieve [1 ]
Chastain, Ashley [1 ]
Wang, Ruipeng [1 ]
Spencer, Matthew [1 ]
He, Biao [1 ]
Stutzman, Nicole [1 ]
Kano, Daiji [1 ]
Arthos, James [2 ]
Fischer, Elizabeth [3 ]
Chun, Tae-Wook [2 ]
Moir, Susan [2 ]
Sun, Peter [1 ]
机构
[1] NIAID, NIH, Lab Immunogenet, 12441 Parklawn Dr, Rockville, MD 20852 USA
[2] NIAID, NIH, Lab Immunoregulat, 9000 Rockville Pike, Bethesda, MD 20892 USA
[3] NIAID, NIH, Res Technol Branch, 903 South 4th St, Hamilton, MT 59840 USA
来源
NATURE COMMUNICATIONS | 2018年 / 9卷
基金
美国国家卫生研究院;
关键词
HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL THERAPY; REPLICATION-COMPETENT HIV; CENTRAL MEMORY; ENVELOPE GLYCOPROTEIN; B-CELLS; PROTEIN; LYMPHOCYTES; EFFECTOR;
D O I
10.1038/s41467-018-05197-2
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
CD4 and chemokine receptors mediate HIV-1 attachment and entry. They are, however, insufficient to explain the preferential viral infection of central memory T cells. Here, we identify L-selectin (CD62L) as a viral adhesion receptor on CD4(+) T cells. The binding of viral envelope glycans to L-selectin facilitates HIV entry and infection, and L-selectin expression on central memory CD4(+) T cells supports their preferential infection by HIV. Upon infection, the virus downregulates L-selectin expression through shedding, resulting in an apparent loss of central memory CD4(+) T cells. Infected effector memory CD4(+) T cells, however, remain competent in cytokine production. Surprisingly, inhibition of L-selectin shedding markedly reduces HIV-1 infection and suppresses viral release, suggesting that L-selectin shedding is required for HIV-1 release. These findings highlight a critical role for cell surface sheddase in HIV-1 pathogenesis and reveal new antiretroviral strategies based on small molecular inhibitors targeted at metalloproteinases for viral release.
引用
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页数:15
相关论文
共 38 条
[31]   HIV-1 Nef Induces Proinflammatory State in Macrophages through Its Acidic Cluster Domain: Involvement of TNF Alpha Receptor Associated Factor 2 [J].
Mangino, Giorgio ;
Percario, Zulema A. ;
Fiorucci, Gianna ;
Vaccari, Gabriele ;
Acconcia, Filippo ;
Chiarabelli, Cristiano ;
Leone, Stefano ;
Noto, Alessia ;
Horenkamp, Florian A. ;
Manrique, Santiago ;
Romeo, Giovanna ;
Polticelli, Fabio ;
Geyer, Matthias ;
Affabris, Elisabetta .
PLOS ONE, 2011, 6 (08)
[32]   Expression of HIV-1 Vpu Leads to Loss of the Viral Restriction Factor CD317/Tetherin from Lipid Rafts and Its Enhanced Lysosomal Degradation [J].
Rollason, Ruth ;
Dunstan, Katie ;
Billcliff, Peter G. ;
Bishop, Paul ;
Gleeson, Paul ;
Wise, Helen ;
Digard, Paul ;
Banting, George .
PLOS ONE, 2013, 8 (09)
[33]   HIV-1 Nef activates proviral DNA transcription by recruiting Src kinase to phosphorylate host protein Nef-associated factor 1 to compromise its viral restrictive function [J].
Fan, Tian-Jiao ;
Xie, Chengzuo ;
Li, Lisha ;
Jin, Xia ;
Cui, Jie ;
Wang, Jian-Hua .
JOURNAL OF VIROLOGY, 2025,
[34]   HIV-1 Glycoprotein 41 Ectodomain Induces Activation of the CD74 Protein-mediated Extracellular Signal-regulated Kinase/Mitogen-activated Protein Kinase Pathway to Enhance Viral Infection [J].
Zhou, Chang ;
Lu, Lu ;
Tan, Suiyi ;
Jiang, Shibo ;
Chen, Ying-Hua .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (52) :44869-44877
[35]   Fusion to Flaviviral Leader Peptide Targets HIV-1 Reverse Transcriptase for Secretion and Reduces Its Enzymatic Activity and Ability to Induce Oxidative Stress but Has No Major Effects on Its Immunogenic Performance in DNA-Immunized Mice [J].
Latanova, Anastasia ;
Petkov, Stefan ;
Kuzmenko, Yulia ;
Kilpelainen, Athina ;
Ivanov, Alexander ;
Smirnova, Olga ;
Krotova, Olga ;
Korolev, Sergey ;
Hinkula, Jorma ;
Karpov, Vadim ;
Isaguliants, Maria ;
Starodubova, Elizaveta .
JOURNAL OF IMMUNOLOGY RESEARCH, 2017, 2017
[36]   Viral surface glycoproteins, gp120 and gp41, as potential drug targets against HIV-1: Brief overview one quarter of a century past the approval of zidovudine, the first anti-retroviral drug [J].
Teixeira, Catia ;
Gomes, Jose R. B. ;
Gomes, Paula ;
Maurel, Francois .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2011, 46 (04) :979-992
[37]   Vaccination with a Fusion Protein That Introduces HIV-1 Gag Antigen into a Multitrimer CD40L Construct Results in Enhanced CD8+ T Cell Responses and Protection from Viral Challenge by Vaccinia-Gag [J].
Gupta, Sachin ;
Termini, James M. ;
Raffa, Francesca N. ;
Williams, Cindi-Ann ;
Kornbluth, Richard S. ;
Stone, Geoffrey W. .
JOURNAL OF VIROLOGY, 2014, 88 (03) :1492-1501
[38]   Simultaneous determination of L-702,007, a HIV-1 reverse transcriptase inhibitor, and its 6-hydroxy metabolite in human plasma by column-switching high-performance liquid chromatography with fluorescence detection [J].
Woolf, EJ ;
Matuszewski, B .
JOURNAL OF CHROMATOGRAPHY A, 1996, 729 (1-2) :211-217