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

Nature Communications
Joseph KononchikPeter Sun

Abstract

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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Citations

Mar 1, 2019·Chembiochem : a European Journal of Chemical Biology·Hiroyuki ShinchiYasuo Suda
May 30, 2019·Frontiers in Immunology·Aleksandar IveticSamuel James Hart
Jan 5, 2021·Frontiers in Cardiovascular Medicine·Ahmad Aljohmani, Daniela Yildiz
Jan 23, 2021·Clinical Science·Maria A PedrosaAna I Rodriguez-Perez
Feb 3, 2021·Protein Expression and Purification·Zhongcheng ZouPeter D Sun
Jul 31, 2021·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Rita FolcarelliOscar F van den Brink

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Methods Mentioned

BETA
glycosylations
surface plasmon resonance
enzyme-linked immunosorbent assay
ELISA
PCR
flow cytometry
PMA
transmission electron microscopy
confocal microscopy
Assay

Software Mentioned

Prism
BIAevaluation
FIJI
GraphPad
Huygens Essential
FlowJo

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