TY - JOUR
T1 - Degranulation of natural killer cells following interaction with HIV-1-infected cells is hindered by downmodulation of NTB-A by Vpu
AU - Shah, Ankur H.
AU - Sowrirajan, Bharatwaj
AU - Davis, Zachary B.
AU - Ward, Jeffrey P.
AU - Campbell, Edward M.
AU - Planelles, Vicente
AU - Barker, Edward
N1 - Funding Information:
The authors would like to thank Dr. Alessandro Moretta, University of Genoa, Genoa, Italy, for providing us with the ON56 clone of anti-NTB-A antibody. This work was supported by grants from NIH/NIAID: AI65361 and AI81684 for E.B. and AI49057 and AI81684 for V.P.
PY - 2010/11/18
Y1 - 2010/11/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78349264184&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2010.10.008
DO - 10.1016/j.chom.2010.10.008
M3 - Article
C2 - 21075351
AN - SCOPUS:78349264184
SN - 1931-3128
VL - 8
SP - 397
EP - 409
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 5
ER -