ArticleRetrovirology2012
CD8+ and CD4+ cytotoxic T cell escape mutations precede breakthrough SIVmac239 viremia in an elite controller.
Article in Retrovirology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment: interim analysis from a phase II clinical trial.AIDS research and therapy · 2022Trial
- CD8ɑ+ cells suppress SIV replication without the development of mutations within MHC class-I-restricted epitopes during post-treatment control.Journal of virology · 2026Article
- CD8ɑ+ cells suppress SIV replication without evidence of viral immune escape during post treatment control.bioRxiv : the preprint server for biology · 2025Article
- Early treatment and PD1 inhibition enhance HIV-specific functionality of follicular CD8+ T cells.JCI insight · 2025Article
- Preferential selection of viral escape mutants by CD8+ T cell 'sieving' of SIV reactivation from latency.PLoS pathogens · 2023Article
- Immunotherapy-induced cytotoxic T follicular helper cells reduce numbers of retrovirus-infected reservoir cells in B cell follicles.PLoS pathogens · 2023Article
- Learning to Be Elite: Lessons From HIV-1 Controllers and Animal Models on Trained Innate Immunity and Virus Suppression.Frontiers in immunology · 2022Review
- Myelin-specific T cells in animals with Japanese macaque encephalomyelitis.Annals of clinical and translational neurology · 2021Article
- Diminished Peripheral CD29hi Cytotoxic CD4+ T Cells Are Associated With Deleterious Effects During SIV Infection.Frontiers in immunology · 2021Article
- Mechanisms of Abrupt Loss of Virus Control in a Cohort of Previous HIV Controllers.Journal of virology · 2019Article
- Acute-Phase CD4Journal of virology · 2018Article
- Evidence of CD4Scientific reports · 2018Article
- Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection.Journal of virology · 2018Article
- MR1-restricted mucosal-associated invariant T (MAIT) cells respond to mycobacterial vaccination and infection in nonhuman primates.Mucosal immunology · 2017Article
- HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II TetramerJournal of virology · 2017Article
- Cytotoxic CD4 T Cells-Friend or Foe during Viral Infection?Frontiers in immunology · 2017Review
- Two-Year Follow-Up of Macaques Developing Intermittent Control of the Human Immunodeficiency Virus Homolog Simian Immunodeficiency Virus SIVmac251 in the Chronic Phase of Infection.Journal of virology · 2015Article
- HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses.PLoS pathogens · 2015Article
- Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia.Journal of virology · 2015Article
- Innate and Adaptive Immunity in Long-Term Non-Progression in HIV Disease.Frontiers in immunology · 2013Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundVirus-specific T cells are critical components in the containment of immunodeficiency virus infections. While the protective role of CD8+ T cells is well established by studies of CD8+ T cell-mediated viral escape, it remains unknown if CD4+ T cells can also impose sufficient selective pressure on replicating virus to drive the emergence of high-frequency escape variants. Identifying a high frequency CD4+ T cell driven escape mutation would provide compelling evidence of direct immunological pressure mediated by these cells.
resultsHere, we studied a SIVmac239-infected elite controller rhesus macaque with a 1,000-fold spontaneous increase in plasma viral load that preceded disease progression and death from AIDS-related complications. We sequenced the viral genome pre- and post-breakthrough and demonstrate that CD8+ T cells drove the majority of the amino acid substitutions outside of Env. However, within a region of Gag p27CA targeted only by CD4+ T cells, we identified a unique post-breakthrough mutation, Gag D205E, which abrogated CD4+ T cell recognition. Further, we demonstrate that the Gag p27CA-specific CD4+ T cells exhibited cytolytic activity and that SIV bearing the Gag D205E mutation escapes this CD4+ T cell effector function ex vivo.
conclusionsCumulatively, these results confirm the importance of virus specific CD8+ T cells and demonstrate that CD4+ T cells can also exert significant selective pressure on immunodeficiency viruses in vivo during low-level viral replication. These results also suggest that further studies of CD4+ T cell escape should focus on cases of elite control with spontaneous viral breakthrough.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.