Long-Term Spontaneous Control of HIV-1 Is Related to Low Frequency of Infected Cells and Inefficient Viral Reactivation

Autor: Olivier Lambotte, Gianfranco Pancino, Javier Martinez-Picado, Camille Lécuroux, Ruth Peña, Annie David, Julia G. Prado, Carine Van Lint, Alain Venet, Itziar Erkizia, Véronique Avettand-Fenoel, Nicolas Noel, Esther Jimenez, Faroudy Boufassa, Asier Sáez-Cirión, Christine Rouzioux
Přispěvatelé: Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), IrsiCaixa (Institut de Recerca de la Sida), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), U1018, Institut National de la Santé et de la Recherche Médicale (INSERM), Régulation des Infections Rétrovirales, Service de Virologie Moléculaire, IBMM, Université Libre de Bruxelles, Université libre de Bruxelles (ULB), Institució Catalana de Recerca i Estudis Avançats (ICREA), Universitat de Vic, This work was funded by Agence Nationale de Recherches sur le Sida et les Hepatites Virales (ANRS) (2011409). This work, including the efforts of Nicolas Noel, was funded by Foundation pour la Recherche Medicale (PhD grant). This work, including the efforts of Julia G. Prado, was funded by ISCIII (Miguel Servet II [CIIP15/00014], PI11/00249, and PI14/01058). This work, including the efforts of Carine Van Lint, was funded by Belgian Fund for Scientific Research (FRS-FNRS).This work, including the efforts of Esther Jimenez, was funded by Redes Temáticas de Investigación en SIDA, Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008-2011, and Instituto de Salud Carlos III, Fondos FEDER (ISCIII RETIC RD12/0017/0002), ANRS CO21 Cohort, Saez-Cirion, Asier, HIV, Inflammation et persistance, Institut Pasteur [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris-Sud - Paris 11 (UP11) - Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale, Université Libre de Bruxelles [Bruxelles] (ULB)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Journal of Virology
Journal of Virology, 2016, 90 (13), pp.6148-6158. ⟨10.1128/JVI.00419-16⟩
Journal of Virology, American Society for Microbiology, 2016, 90 (13), pp.6148-6158. ⟨10.1128/JVI.00419-16⟩
Journal of Virology, American Society for Microbiology, 2016, 90 (13), pp.6148-6158. 〈10.1128/JVI.00419-16〉
ISSN: 0022-538X
1098-5514
Popis: HIV establishes reservoirs of infected cells that persist despite effective antiretroviral therapy (ART). In most patients, the virus begins to replicate soon after treatment interruption. However, a low frequency of infected cells at the time of treatment interruption has been associated with delayed viral rebound. Likewise, individuals who control the infection spontaneously, so-called HIV-1 controllers (HICs), carry particularly low levels of infected cells. It is unclear, however, whether and how this small number of infected cells contributes to durable viral control. Here we compared 38 HICs with 12 patients on effective combined antiretroviral therapy (cART) and found that the low frequency of infected cells in the former subjects was associated both with less efficient viral reactivation in resting CD4 + T cells and with less efficient virion production ex vivo . We also found that a potent HIV-specific CD8 + T cell response was present only in those HICs whose CD4 + T cells produced virus ex vivo . Long-term spontaneous control of HIV infection in HICs thus appears to be sustained on the basis of the inefficient reactivation of viruses from a limited number of infected cells and the capacity of HICs to activate a potent HIV-specific CD8 + T cell response to counteract efficient viral reactivation events. IMPORTANCE There is a strong scientific interest in developing strategies to eradicate the HIV-1 reservoir. Very rare HIV-1-infected patients are able to spontaneously control viremia for long periods of time (HIV-1 controllers [HICs]) and are put forward as a model of HIV-1 remission. Here, we show that the low viral reservoirs found in HICs are a critical part of the mechanisms underlying viral control and result in a lower probability of HIV-1 reactivation events, resulting in limited HIV-1 release and spread. We found that those HICs in whom viral reactivation and spread from CD4 + T cells in vitro were the most difficult were those with diminished CD8 + T cell responses. These results suggest that, in some settings, low HIV-1 reservoirs decisively contribute to at least the temporary control of infection without antiretroviral therapy. We believe that this work provides information of relevance in the context of the search for HIV-1 remission.
Databáze: OpenAIRE
Externí odkaz: