Suppression of HIV-1 Nef translation by Sam68 mutant-induced stress granules and nef mRNA sequestration.
Mol Cell
; 33(1): 87-96, 2009 Jan 16.
Article
em En
| MEDLINE
| ID: mdl-19150430
ABSTRACT
HIV-1 Nef plays important roles in HIV-1 replication and pathogenesis. It is translated from completely spliced HIV-1 RNA, and its expression is inherently regulated at the levels of viral DNA transcription and RNA splicing. Here we show that Sam68 cytoplasmic mutants potently suppress Nef expression. The suppression requires Sam68 domain aa 269-321 and is correlated with its ability to induce stress granules. In addition, the suppression is specific to Nef, and direct binding to nef mRNA 3'UTR confers the suppression specificity. Furthermore, nef mRNA is targeted to and enriched in these induced stress granules. Importantly, Nef suppression occurs in the context of HIV-1 infection of CD4+ T lymphocytes with little MHC I and CD4 downregulation. Taken together, these results demonstrate that stress granule induction and nef mRNA sequestration account for this translational suppression of Nef expression and offer a strategy for development of anti-HIV therapeutics to buttress our fight against HIV/AIDS.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biossíntese de Proteínas
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HIV-1
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Proteínas de Ligação a RNA
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Grânulos Citoplasmáticos
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas de Ligação a DNA
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Produtos do Gene nef do Vírus da Imunodeficiência Humana
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Mutação
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos