Cell Surface Downregulation of NK Cell Ligands by Patient-Derived HIV-1 Vpu and Nef Alleles
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Cell Surface Downregulation of NK Cell Ligands by Patient-Derived HIV-1 Vpu and Nef Alleles. / Galaski, Johanna; Ahmad, Fareed; Tibroni, Nadine; Pujol, Francois M; Müller, Birthe; Schmidt, Reinhold E; Fackler, Oliver T.
In: JAIDS-J ACQ IMM DEF, Vol. 72, No. 1, 01.05.2016, p. 1-10.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cell Surface Downregulation of NK Cell Ligands by Patient-Derived HIV-1 Vpu and Nef Alleles
AU - Galaski, Johanna
AU - Ahmad, Fareed
AU - Tibroni, Nadine
AU - Pujol, Francois M
AU - Müller, Birthe
AU - Schmidt, Reinhold E
AU - Fackler, Oliver T
PY - 2016/5/1
Y1 - 2016/5/1
N2 - OBJECTIVE: HIV-1 Vpu and Nef proteins downregulate cell surface levels of natural killer (NK) cell ligands but functional consequences of individual downregulation events are unclear. We tested how well-conserved NK cell ligand downregulation is among Vpu and Nef variants isolated from chronic HIV patients.METHODS: Proviral vpu and nef sequences were amplified from 27 chronic HIV patients, subcloned, and tested for their ability to downregulate cell surface receptors.RESULTS: Cell surface downregulation of CD4, CD317/tetherin, and major histocompatibility complex class 1 that exert biological functions other than NK cell activation were well conserved among patient-derived Vpu and Nef variants. Among NK cell ligands, NK-T-B-antigen, poliovirus receptor, and UL16-binding protein were identified as main targets for Vpu and Nef, the downregulation of which by at least 1 viral protein was highly conserved. NK cell ligands displayed specific sensitivity to Vpu (NK-T-B-antigen) or Nef (poliovirus receptor), and downregulation of cell surface UL16-binding protein was identified as a novel and highly conserved activity of HIV-1 Vpu but not Nef.CONCLUSIONS: The conservation of downregulation of major NK cell ligands by either HIV-1 Vpu or Nef suggests an important pathophysiological role of this activity, which may impact the acute but not the chronic phase of HIV infection.
AB - OBJECTIVE: HIV-1 Vpu and Nef proteins downregulate cell surface levels of natural killer (NK) cell ligands but functional consequences of individual downregulation events are unclear. We tested how well-conserved NK cell ligand downregulation is among Vpu and Nef variants isolated from chronic HIV patients.METHODS: Proviral vpu and nef sequences were amplified from 27 chronic HIV patients, subcloned, and tested for their ability to downregulate cell surface receptors.RESULTS: Cell surface downregulation of CD4, CD317/tetherin, and major histocompatibility complex class 1 that exert biological functions other than NK cell activation were well conserved among patient-derived Vpu and Nef variants. Among NK cell ligands, NK-T-B-antigen, poliovirus receptor, and UL16-binding protein were identified as main targets for Vpu and Nef, the downregulation of which by at least 1 viral protein was highly conserved. NK cell ligands displayed specific sensitivity to Vpu (NK-T-B-antigen) or Nef (poliovirus receptor), and downregulation of cell surface UL16-binding protein was identified as a novel and highly conserved activity of HIV-1 Vpu but not Nef.CONCLUSIONS: The conservation of downregulation of major NK cell ligands by either HIV-1 Vpu or Nef suggests an important pathophysiological role of this activity, which may impact the acute but not the chronic phase of HIV infection.
KW - Alleles
KW - Antigens, CD
KW - CD4 Antigens
KW - Cell Line, Tumor
KW - Down-Regulation
KW - GPI-Linked Proteins
KW - HIV Infections
KW - HIV-1
KW - HeLa Cells
KW - Histocompatibility Antigens Class I
KW - Human Immunodeficiency Virus Proteins
KW - Humans
KW - Intercellular Signaling Peptides and Proteins
KW - Killer Cells, Natural
KW - Ligands
KW - Receptors, Natural Killer Cell
KW - Receptors, Virus
KW - Viral Regulatory and Accessory Proteins
KW - nef Gene Products, Human Immunodeficiency Virus
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1097/QAI.0000000000000917
DO - 10.1097/QAI.0000000000000917
M3 - SCORING: Journal article
C2 - 26656785
VL - 72
SP - 1
EP - 10
JO - JAIDS-J ACQ IMM DEF
JF - JAIDS-J ACQ IMM DEF
SN - 1525-4135
IS - 1
ER -