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Broadening of Virus-Specific CD8 T-Cell Responses Is Indicative of Residual Viral Replication in Aviremic SIV Controllers


CD8+ T-cell responses are crucial for HIV control, but it is unclear whether lasting HIV containment can be achieved after establishment of infection. Several T cell-based vaccine trials have currently shown primary viremia control in macaque AIDS models of simian immunodeficiency virus (SIV) infection, but residual viral replication may occur, followed by accumulation of viral CD8+ T-cell escape mutations, possibly leading to eventual viremia rebound. In the present study, we analyzed ten rhesus macaques that controlled SIV replication without detectable viremia for more than 2 years. Animals were divided into two groups on the basis of proviral genome sequences at 2 years post-infection. Analysis of the first group exhibiting multiple CD8+ T-cell escape mutations indicated that broadening of CD8+ T-cell responses can be an indicator of the beginning of viral control failure. Conversely, analysis of the second group having no mutation suggested that stability of the breadth of virus-specific CD8+ T-cell responses represents a status of lasting HIV containment by CD8+ T cells. Thus, this study presents a model of stable SIV containment, contributing to elucidation of the requisites for lasting HIV control.


Vyšlo v časopise: Broadening of Virus-Specific CD8 T-Cell Responses Is Indicative of Residual Viral Replication in Aviremic SIV Controllers. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005247
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005247

Souhrn

CD8+ T-cell responses are crucial for HIV control, but it is unclear whether lasting HIV containment can be achieved after establishment of infection. Several T cell-based vaccine trials have currently shown primary viremia control in macaque AIDS models of simian immunodeficiency virus (SIV) infection, but residual viral replication may occur, followed by accumulation of viral CD8+ T-cell escape mutations, possibly leading to eventual viremia rebound. In the present study, we analyzed ten rhesus macaques that controlled SIV replication without detectable viremia for more than 2 years. Animals were divided into two groups on the basis of proviral genome sequences at 2 years post-infection. Analysis of the first group exhibiting multiple CD8+ T-cell escape mutations indicated that broadening of CD8+ T-cell responses can be an indicator of the beginning of viral control failure. Conversely, analysis of the second group having no mutation suggested that stability of the breadth of virus-specific CD8+ T-cell responses represents a status of lasting HIV containment by CD8+ T cells. Thus, this study presents a model of stable SIV containment, contributing to elucidation of the requisites for lasting HIV control.


Zdroje

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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