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

被引：16

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

页数：15