Nef defect attenuates HIV viremia and immune dysregulation in the bone marrow-liver-thymus-spleen (BLTS) humanized mouse model.
Virology
; 598: 110192, 2024 Oct.
Article
em En
| MEDLINE
| ID: mdl-39106585
ABSTRACT
In vitro studies have shown that deletion of nef and deleterious mutation in the Nef dimerization interface attenuates HIV replication and associated pathogenesis. Humanized rodents with human immune cells and lymphoid tissues are robust in vivo models for investigating the interactions between HIV and the human immune system. Here, we demonstrate that nef deletion impairs HIV replication and HIV-induced immune dysregulation in the blood and human secondary lymphoid tissue (human spleen) in bone marrow-liver-thymus-spleen (BLTS) humanized mice. Furthermore, we also show that nef defects (via deleterious mutations in the dimerization interface) impair HIV replication and HIV-induced immune dysregulation in the blood and human spleen in BLTS-humanized mice. We demonstrate that the reduced replication of nef-deleted and nef-defective HIV is associated with robust antiviral innate immune response, and T helper 1 response. Our results support the proposition that Nef may be a therapeutic target for adjuvants in HIV cure strategies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Baço
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Viremia
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Replicação Viral
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Infecções por HIV
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HIV-1
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Modelos Animais de Doenças
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Produtos do Gene nef do Vírus da Imunodeficiência Humana
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Fígado
Limite:
Animals
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Humans
Idioma:
En
Revista:
Virology
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos