Cell Surface Downregulation of NK Cell Ligands by Patient-Derived HIV-1 Vpu and Nef Alleles
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. Pr...
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Published in | Journal of acquired immune deficiency syndromes (1999) Vol. 72; no. 1; p. 1 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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United States
01.05.2016
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Abstract | 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.
Proviral vpu and nef sequences were amplified from 27 chronic HIV patients, subcloned, and tested for their ability to downregulate cell surface receptors.
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.
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. |
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AbstractList | 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.
Proviral vpu and nef sequences were amplified from 27 chronic HIV patients, subcloned, and tested for their ability to downregulate cell surface receptors.
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.
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. |
Author | Ahmad, Fareed Galaski, Johanna Fackler, Oliver T Pujol, Francois M Tibroni, Nadine Müller, Birthe Schmidt, Reinhold E |
Author_xml | – sequence: 1 givenname: Johanna surname: Galaski fullname: Galaski, Johanna organization: Department of Infectious Diseases, Integrative Virology, University Hospital Heidelberg, Heidelberg, Germany; †German Center for Infection Research, Heidelberg University, Heidelberg, Germany; ‡Department of Clinical Immunology and Rheumatology, Hannover Medical School, Hannover, Germany; and §German Center for Infection Research, Hannover Medical School, Hannover, Germany – sequence: 2 givenname: Fareed surname: Ahmad fullname: Ahmad, Fareed – sequence: 3 givenname: Nadine surname: Tibroni fullname: Tibroni, Nadine – sequence: 4 givenname: Francois M surname: Pujol fullname: Pujol, Francois M – sequence: 5 givenname: Birthe surname: Müller fullname: Müller, Birthe – sequence: 6 givenname: Reinhold E surname: Schmidt fullname: Schmidt, Reinhold E – sequence: 7 givenname: Oliver T surname: Fackler fullname: Fackler, Oliver T |
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SubjectTerms | Alleles Antigens, CD - biosynthesis CD4 Antigens - biosynthesis Cell Line, Tumor Down-Regulation GPI-Linked Proteins - biosynthesis HeLa Cells Histocompatibility Antigens Class I - biosynthesis HIV Infections - virology HIV-1 - genetics Human Immunodeficiency Virus Proteins - genetics Humans Intercellular Signaling Peptides and Proteins - biosynthesis Killer Cells, Natural - immunology Ligands nef Gene Products, Human Immunodeficiency Virus - genetics Receptors, Natural Killer Cell - biosynthesis Receptors, Virus - biosynthesis Viral Regulatory and Accessory Proteins - genetics |
Title | Cell Surface Downregulation of NK Cell Ligands by Patient-Derived HIV-1 Vpu and Nef Alleles |
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