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. HIV binding is mediated via CD4 and chemokine co-receptors, but this does not explain the preferential infection of central memory CD4+ T cells. Here the authors show HIV targets L-selectin, induces shedding from the infected cell, and inhibition of L-selectin reduces HIV infection and release.
HIV-1 targets L-selectin for adhesion and induces its shedding for viral release
[Category] E형 간염,
[Article Type] Article
[Source] PMC
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