Cell Surface Downregulation of NK Cell Ligands by Patient-Derived HIV-1 Vpu and Nef Alleles.
J Acquir Immune Defic Syndr
; 72(1): 1-10, 2016 May 01.
Article
em En
| MEDLINE
| ID: mdl-26656785
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Virais
/
Células Matadoras Naturais
/
Peptídeos e Proteínas de Sinalização Intercelular
/
Produtos do Gene nef do Vírus da Imunodeficiência Humana
/
Proteínas do Vírus da Imunodeficiência Humana
/
Proteínas Virais Reguladoras e Acessórias
/
Receptores de Células Matadoras Naturais
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Acquir Immune Defic Syndr
Ano de publicação:
2016
Tipo de documento:
Article