Cell surface downregulation of NK cell ligands by patient-derived HIV-1 Vpu and Nef alleles

• Verfasst von: Galaski, Johanna [VerfasserIn]
• Verfasst von: Tibroni, Nadine [VerfasserIn]
• Verfasst von: Pujol, Franc̦ois [VerfasserIn]
• Verfasst von: Müller, Birthe [VerfasserIn]
• Verfasst von: Fackler, Oliver Till [VerfasserIn]
• Titel: Cell surface downregulation of NK cell ligands by patient-derived HIV-1 Vpu and Nef alleles
• Verf.angabe: Johanna Galaski, Fareed Ahmad, PhD, Nadine Tibroni, Francois M. Pujol, PhD, Birthe Müller, MA, Reinhold E. Schmidt, MD, and Oliver T. Fackler, PhD
• E-Jahr: 2016
• Jahr: May 2016
• Umfang: 10 S.
• Fussnoten: Gesehen am 25.10.2019
• Titel Quelle: Enthalten in: Journal of acquired immune deficiency syndromes
• Ort Quelle: Philadelphia, Pa. : Lippincott Williams & Wilkins, 1996
• Jahr Quelle: 2016
• Band/Heft Quelle: 72(2016), 1, Seite 1-10
• ISSN Quelle: 1944-7884
• ISSN Quelle: 1077-9450
• DOI: doi:10.1097/QAI.0000000000000917
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1680014250

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.