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

Joseph Kononchik, Joanna Ireland, Zhongcheng Zou, Jason Segura, Genevieve Holzapfel, Ashley Chastain, Ruipeng Wang, Matthew Spencer, Biao He, Nicole Stutzman, Daiji Kano, James Arthos, Elizabeth Fischer, Tae-Wook Chun, Susan Moir and Peter Sun ()
Additional contact information
Joseph Kononchik: National Institutes of Health
Joanna Ireland: National Institutes of Health
Zhongcheng Zou: National Institutes of Health
Jason Segura: National Institutes of Health
Genevieve Holzapfel: National Institutes of Health
Ashley Chastain: National Institutes of Health
Ruipeng Wang: National Institutes of Health
Matthew Spencer: National Institutes of Health
Biao He: National Institutes of Health
Nicole Stutzman: National Institutes of Health
Daiji Kano: National Institutes of Health
James Arthos: National Institutes of Health
Elizabeth Fischer: National Institutes of Health
Tae-Wook Chun: National Institutes of Health
Susan Moir: National Institutes of Health
Peter Sun: National Institutes of Health

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05197-2

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