title: Degranulation of natural killer cells following interaction with HIV-1-infected cells is hindered by downmodulation of NTB-A by Vpu.
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.
authors.affiliation: Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Ankur H
authors.initials: AH
authors.lastname: Shah
authors.forename: Bharatwaj
authors.initials: B
authors.lastname: Sowrirajan
authors.forename: Zachary B
authors.initials: ZB
authors.lastname: Davis
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Ward
authors.forename: Edward M
authors.initials: EM
authors.lastname: Campbell
authors.forename: Vicente
authors.initials: V
authors.lastname: Planelles
authors.forename: Edward
authors.initials: E
authors.lastname: Barker
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015550:Cell Degranulation; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D054298:Human Immunodeficiency Virus Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011956:Receptors, Cell Surface; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D054334:Viral Regulatory and Accessory Proteins; C000604060:SLAMF6 protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins