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

Nicolas Noel 1 Ruth Peña 2 Annie David 3 Veronique Avettand-Fenoel 4 Itziar Erkizia 2 Esther Jimenez 2 Camille Lecuroux 1 Christine Rouzioux 4 Faroudy Boufassa 5 Gianfranco Pancino 6 Alain Venet 1 Carine van Lint 7 Javier Martinez-Picado 8, 2, 9 Olivier Lambotte 1 Asier Sáez-Cirión 3, * Julia G. Prado 2, *
* Corresponding author
1 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes
2 IrsiCaixa (Institut de Recerca de la Sida)
3 HIV, Inflammation et persistance
4 Laboratoire de Virologie [CHU Necker]
5 U1018
6 Régulation des Infections Rétrovirales
7 Service de Virologie Moléculaire, IBMM, Université Libre de Bruxelles
8 ICREA - Institució Catalana de Recerca i Estudis Avançats
9 Universitat de Vic
Abstract : 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.
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Nicolas Noel, Ruth Peña, Annie David, Veronique Avettand-Fenoel, Itziar Erkizia, et al.. Long-Term Spontaneous Control of HIV-1 Is Related to Low Frequency of Infected Cells and Inefficient Viral Reactivation.. Journal of Virology, American Society for Microbiology, 2016, 90 (13), pp.6148 - 6158. ⟨10.1128/JVI.00419-16⟩. ⟨pasteur-01414933⟩

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