Cell surface downregulation of NK cell ligands by patient-derived HIV-1 Vpu and Nef alleles
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 p...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
May 2016
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| In: |
Journal of acquired immune deficiency syndromes
Year: 2016, Volume: 72, Issue: 1, Pages: 1-10 |
| ISSN: | 1944-7884 |
| DOI: | 10.1097/QAI.0000000000000917 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1097/QAI.0000000000000917 Verlag, Volltext: https://journals.lww.com/jaids/Fulltext/2016/05010/Cell_Surface_Downregulation_of_NK_Cell_Ligands_by.1.aspx#pdf-link 
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| Author Notes: | Johanna Galaski, Fareed Ahmad, PhD, Nadine Tibroni, Francois M. Pujol, PhD, Birthe Müller, MA, Reinhold E. Schmidt, MD, and Oliver T. Fackler, PhD |
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| 245 | 1 | 0 | |a Cell surface downregulation of NK cell ligands by patient-derived HIV-1 Vpu and Nef alleles |c Johanna Galaski, Fareed Ahmad, PhD, Nadine Tibroni, Francois M. Pujol, PhD, Birthe Müller, MA, Reinhold E. Schmidt, MD, and Oliver T. Fackler, PhD |
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| 520 | |a 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. | ||
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