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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.
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页数:15
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