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 journalSCORING: Journal articleResearchpeer-review

Harvard

Galaski, J, Ahmad, F, Tibroni, N, Pujol, FM, Müller, B, Schmidt, RE & Fackler, OT 2016, 'Cell Surface Downregulation of NK Cell Ligands by Patient-Derived HIV-1 Vpu and Nef Alleles', JAIDS-J ACQ IMM DEF, vol. 72, no. 1, pp. 1-10. https://doi.org/10.1097/QAI.0000000000000917

APA

Galaski, J., Ahmad, F., Tibroni, N., Pujol, F. M., Müller, B., Schmidt, R. E., & Fackler, O. T. (2016). Cell Surface Downregulation of NK Cell Ligands by Patient-Derived HIV-1 Vpu and Nef Alleles. JAIDS-J ACQ IMM DEF, 72(1), 1-10. https://doi.org/10.1097/QAI.0000000000000917

Vancouver

Bibtex

@article{b84b3fd88c2a48d39fbc5c24e26a590b,
title = "Cell Surface Downregulation of NK Cell Ligands by Patient-Derived HIV-1 Vpu and Nef Alleles",
abstract = "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.",
keywords = "Alleles, Antigens, CD, CD4 Antigens, Cell Line, Tumor, Down-Regulation, GPI-Linked Proteins, HIV Infections, HIV-1, HeLa Cells, Histocompatibility Antigens Class I, Human Immunodeficiency Virus Proteins, Humans, Intercellular Signaling Peptides and Proteins, Killer Cells, Natural, Ligands, Receptors, Natural Killer Cell, Receptors, Virus, Viral Regulatory and Accessory Proteins, nef Gene Products, Human Immunodeficiency Virus, Journal Article, Research Support, Non-U.S. Gov't",
author = "Johanna Galaski and Fareed Ahmad and Nadine Tibroni and Pujol, {Francois M} and Birthe M{\"u}ller and Schmidt, {Reinhold E} and Fackler, {Oliver T}",
year = "2016",
month = may,
day = "1",
doi = "10.1097/QAI.0000000000000917",
language = "English",
volume = "72",
pages = "1--10",
journal = "JAIDS-J ACQ IMM DEF",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

RIS

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 -