Control of HIV-1 pathogenesis in viremic nonprogressors is independent of Gag-specific CTL responses

Control of HIV-1 pathogenesis in viremic nonprogressors is independent of Gag-specific CTL responses

Online publication: 28/03/2018 Journal: Journal of Virology


Viremic nonprogressors (VNP) constitute a very scarce group of untreated HIV-1-infected individuals who maintain stable CD4+ T cell-counts despite high levels of HIV-1 replication. The specific factors associated to this atypical control of the HIV infection are poorly described. Since specific T-cell responses seem to be one of the main causes of HIV-1 control in elite controllers, herein we study if HIV-1 Gag-specific cytotoxic T lymphocyte (CTL) responses could also modulate disease control in VNP.We characterized immune responses from four VNPs compared to five subjects with standard progression (SP) during the first years of HIV-1 infection. We observed no differences in the breadth and frequency of Gag-specific cellular responses. Furthermore, we obtained 217 HIV-1Gag clonal sequences in which viral variability of Gag increased over 3 years of infection for synonymous and non-synonymous mutations in both VNP and SP. VNPs evolution rates in gag were comparable to SP. This observation is in line with a similar accumulation of CTL putative escape mutations in Gag epitopes targeted by CTL responses.Altogether, the absence of viral pathogenesis in VNP individuals seems to be independent of HIV-Gag-specific CTL-cell responses. This novel information guides to the study of alternative mechanism of HIV-1 pathogenesis control.IMPORTANCE Control of the HIV infection has been widely studied in elite controllers or long-term nonprogressors models. However, there is a less known group of individuals, termed viremic nonprogressors (VNP), who maintain stable CD4+ T-cell counts despite high plasma viremia. The mechanisms involved in this remarkable control of HIV-1 pathogenesis clearly have implications for the development of new drugs and vaccines.We show for the first time that VNPs have similar immune responses and HIV-gag evolution than standard progressors. Remarkably we demonstrate that the mechanism of pathogenesis control in these individuals differs from some elite controllers that are reported to have improved immune control. This is noteworthy as opens the door to, yet unknown, new mechanisms of HIV control.Our novel results advance the understanding of mechanisms involved in the viremic nonprogression and suggest that there are alternative mechanisms to the adaptive immune responses to an effective control of viral pathogenesis.

Authors: Maria Salgado, Albert Garcia-Minambres, Judith Dalmau, Esther Jiménez-Moyano, Pompeyo Viciana, Belén Alejos, Bonaventura Clotet, Julia G. Prado and Javier Martinez-Picado. 

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