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Transcription of HIV-1 at sites of intact latent provirus integration.
Teixeira, Ana Rafaela; Bittar, Cintia; Silva Santos, Gabriela S; Oliveira, Thiago Y; Huang, Amy S; Linden, Noemi; Ferreira, Isabella A T M; Murdza, Tetyana; Muecksch, Frauke; Jones, R Brad; Caskey, Marina; Jankovic, Mila; Nussenzweig, Michel C.
Afiliación
  • Teixeira AR; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Bittar C; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Silva Santos GS; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Oliveira TY; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Huang AS; Tessera Therapeutics, Somerville, MA 02143, USA.
  • Linden N; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
  • Ferreira IATM; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
  • Murdza T; Department of Infectious Diseases, Heidelberg University, Medical Faculty Heidelberg, Virology, Center for Integrative Infectious Disease Research (CIID), Heidelberg, Germany.
  • Muecksch F; Department of Infectious Diseases, Heidelberg University, Medical Faculty Heidelberg, Virology, Center for Integrative Infectious Disease Research (CIID), Heidelberg, Germany.
  • Jones RB; Chica and Heinz Schaller (CHS) Research Group, Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany.
  • Caskey M; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
  • Jankovic M; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Nussenzweig MC; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
bioRxiv ; 2024 Apr 29.
Article en En | MEDLINE | ID: mdl-38746186
ABSTRACT
HIV-1 anti-retroviral therapy is highly effective but fails to eliminate a reservoir of latent proviruses leading to a requirement for life-long treatment. How the site of integration of authentic intact latent proviruses might impact their own or neighboring gene expression or reservoir dynamics is poorly understood. Here we report on proviral and neighboring gene transcription at sites of intact latent HIV-1 integration in cultured T cells obtained directly from people living with HIV, as well as engineered primary T cells and cell lines. Proviral gene expression was correlated to the level of endogenous gene expression under resting but not activated conditions. Notably, latent proviral promoters were 10010,000X less active than in productively infected cells and had little or no measurable impact on neighboring gene expression under resting or activated conditions. Thus, the site of integration has a dominant effect on the transcriptional activity of intact HIV-1 proviruses in the latent reservoir thereby influencing cytopathic effects and proviral immune evasion.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos