Modulation of TCR-dependent NFAT signaling is impaired in HIV-1 Nef isolates from elite controllers.
Virology
; 530: 39-50, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30780124
HIV-1 Nef modulates the activation state of CD4+ T cells by altering signaling events elicited by the T cell receptor (TCR). Primary nef sequences exhibit extensive inter-individual diversity that influences their ability to downregulate CD4 and HLA class I; however, the impact of nef variation on modulation of T cell signaling is poorly characterized. Here, we measured TCR-mediated activation of NFAT transcription factor in the presence of nef alleles isolated from 45 elite controllers (EC) and 46 chronic progressors (CP). EC Nef clones displayed lower ability to inhibit NFAT signaling (median 87 [IQR 75-93]% relative to SF2 Nef) compared to CP clones (94 [IQR 89-98]%) (pâ¯<â¯0.001). Polymorphisms in Nef's N-terminal domain impaired its ability to inhibit NFAT signaling. Results indicate that primary nef alleles exhibit a range of abilities to modulate TCR-dependent NFAT signaling, implicating natural variation in this function as a potential contributor to differential HIV-1 pathogenesis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
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Transdução de Sinais
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Infecções por HIV
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Sobreviventes de Longo Prazo ao HIV
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Fatores de Transcrição NFATC
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Produtos do Gene nef do Vírus da Imunodeficiência Humana
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Interações Hospedeiro-Patógeno
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article