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Clonal CD4+ T cells in the HIV-1 latent reservoir display a distinct gene profile upon reactivation.
Cohn, Lillian B; da Silva, Israel T; Valieris, Renan; Huang, Amy S; Lorenzi, Julio C C; Cohen, Yehuda Z; Pai, Joy A; Butler, Allison L; Caskey, Marina; Jankovic, Mila; Nussenzweig, Michel C.
Afiliação
  • Cohn LB; Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA.
  • da Silva IT; Laboratory of Computational Biology and Bioinformatics, A.C. Camargo Cancer Center (CIPE), Sao Paulo, Brazil.
  • Valieris R; Laboratory of Computational Biology and Bioinformatics, A.C. Camargo Cancer Center (CIPE), Sao Paulo, Brazil.
  • Huang AS; Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA.
  • Lorenzi JCC; Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA.
  • Cohen YZ; Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA.
  • Pai JA; Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA.
  • Butler AL; Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA.
  • Caskey M; Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA.
  • Jankovic M; Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA.
  • Nussenzweig MC; Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA. nussen@rockefeller.edu.
Nat Med ; 24(5): 604-609, 2018 05.
Article em En | MEDLINE | ID: mdl-29686423
ABSTRACT
Despite suppressive combination antiretroviral therapy (ART), latent HIV-1 proviruses persist in patients. This latent reservoir is established within 48-72 h after infection, has a long half-life1,2, enables viral rebound when ART is interrupted, and is the major barrier to a cure for HIV-1 3 . Latent cells are exceedingly rare in blood (∼1 per 1 × 106 CD4+ T cells) and are typically enumerated by indirect means, such as viral outgrowth assays4,5. We report a new strategy to purify and characterize single reactivated latent cells from HIV-1-infected individuals on suppressive ART. Surface expression of viral envelope protein was used to enrich reactivated latent T cells producing HIV RNA, and single-cell analysis was performed to identify intact virus. Reactivated latent cells produce full-length viruses that are identical to those found in viral outgrowth cultures and represent clones of in vivo expanded T cells, as determined by their T cell receptor sequence. Gene-expression analysis revealed that these cells share a transcriptional profile that includes expression of genes implicated in silencing the virus. We conclude that reactivated latent T cells isolated from blood can share a gene-expression program that allows for cell division without activation of the cell death pathways that are normally triggered by HIV-1 replication.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / HIV-1 / Latência Viral / Perfilação da Expressão Gênica Limite: Humans Idioma: En Revista: Nat Med Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / HIV-1 / Latência Viral / Perfilação da Expressão Gênica Limite: Humans Idioma: En Revista: Nat Med Ano de publicação: 2018 Tipo de documento: Article