HIV-1 Balances the Fitness Costs and Benefits of Disrupting the Host Cell Actin Cytoskeleton Early after Mucosal Transmission.
Cell Host Microbe
; 25(1): 73-86.e5, 2019 01 09.
Article
em En
| MEDLINE
| ID: mdl-30629922
ABSTRACT
HIV-1 primarily infects T lymphocytes and uses these motile cells as migratory vehicles for effective dissemination in the host. Paradoxically, the virus at the same time disrupts multiple cellular processes underlying lymphocyte motility, seemingly counterproductive to rapid systemic infection. Here we show by intravital microscopy in humanized mice that perturbation of the actin cytoskeleton via the lentiviral protein Nef, and not changes to chemokine receptor expression or function, is the dominant cause of dysregulated infected T cell motility in lymphoid tissue by preventing stable cellular polarization required for fast migration. Accordingly, disrupting the Nef hydrophobic patch that facilitates actin cytoskeletal perturbation initially accelerates systemic viral dissemination after female genital transmission. However, the same feature of Nef was subsequently critical for viral persistence in immune-competent hosts. Therefore, a highly conserved activity of lentiviral Nef proteins has dual effects and imposes both fitness costs and benefits on the virus at different stages of infection.
Palavras-chave
Texto completo:
1
Temas:
ECOS
/
Financiamentos_gastos
Bases de dados:
MEDLINE
Assunto principal:
Citoesqueleto de Actina
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Infecções por HIV
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Movimento Celular
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HIV-1
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Mucosa
Tipo de estudo:
Health_economic_evaluation
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cell Host Microbe
Assunto da revista:
MICROBIOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos