Degranulation of natural killer cells following interaction with HIV-1-infected cells is hindered by downmodulation of NTB-A by Vpu

Ankur H. Shah, Bharatwaj Sowrirajan, Zachary B. Davis, Jeffrey P. Ward, Edward M. Campbell, Vicente Planelles, Edward Barker

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

Natural killer (NK) cell degranulation in response to virus-infected cells is triggered by interactions between invariant NK cell surface receptors and their ligands on target cells. Although HIV-1 Vpr induces expression of ligands for NK cell activation receptor, NKG2D, on infected cells, this is not sufficient to promote lytic granule release. We show that triggering the NK cell coactivation receptor NK-T- and -B cell antigen (NTB-A) alongside NKG2D promotes NK cell degranulation. Normally, NK cell surface NTB-A binds to NTB-A on CD4+ T cells. However, HIV-1 Vpu downmodulates NTB-A on infected T cells. Vpu associates with NTB-A through its transmembrane region without promoting NTB-A degradation. Cells infected with HIV-1 Vpu mutant elicited at least 50% more NK cells to degranulate than wild-type virus. Moreover, NK cells have a higher capacity to lyse HIV-infected cells with a mutant Vpu. Thus, Vpu downmodulation of NTB-A protects the infected cell from lysis by NK cells.

Original languageEnglish (US)
Pages (from-to)397-409
Number of pages13
JournalCell Host and Microbe
Volume8
Issue number5
DOIs
StatePublished - Nov 18 2010
Externally publishedYes

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