{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:20:25Z","timestamp":1788848425682,"version":"build-2803163510"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Spontaneous control of chronic-phase HIV\/SIV viremia is often associated with the expression of specific MHC class I allotypes. HIV\/SIV-specific CD8+ cytotoxic T lymphocytes (CTLs) restricted by these MHC class I allotypes appear to be critical for viremic control. Establishment of the elite controller (EC) phenotype is predictable in SIVmac239-infected Indian rhesus macaques (RMs), with approximately 50% of <jats:italic>Mamu-B*08<\/jats:italic>+ RMs and 20% of <jats:italic>Mamu-B*17<\/jats:italic>+ RMs becoming ECs. Despite extensive characterization of EC-associated CTLs in HIV\/SIV-infected individuals, the precise mechanistic basis of elite control remains unknown. Because EC and non-EC viral load trajectories begin diverging by day 14 post-infection, we hypothesized that hyperacute innate immune responses may contribute to viremic control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To gain insight into the immunological factors involved in the determination of EC status, we vaccinated 16 <jats:italic>Mamu-B*08<\/jats:italic>+ RMs with Vif and Nef to elicit EC-associated CTLs, then subjected these 16 vaccinees and an additional 16 unvaccinated <jats:italic>Mamu-B*08<\/jats:italic>+ controls to repeated intrarectal SIVmac239 challenges. We then performed whole-blood transcriptomic analysis of all 32 SIVmac239-infected <jats:italic>Mamu-B*08<\/jats:italic>+ RMs and eight SIVmac239-infected <jats:italic>Mamu-B*08<\/jats:italic><jats:sup>\u2013<\/jats:sup> RMs during the first 14 days of infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Vaccination did not provide protection against acquisition, but peak and setpoint viremia were significantly lower in vaccinees relative to controls. We did not identify any meaningful correlations between vaccine-induced CTL parameters and SIVmac239 acquisition rate or chronic-phase viral loads. Ultimately, 13 of 16 vaccinees (81%) and 7 of 16 controls (44%) became ECs (viremia \u2264 10,000 vRNA copies\/mL plasma for \u2265 4 weeks). We identified subsets of immunomodulatory genes differentially expressed (DE) between RM groupings based on vaccination status, EC status, and MHC class I genotype. These DE genes function in multiple innate immune processes, including the complement system, cytokine\/chemokine signaling, pattern recognition receptors, and interferon-mediated responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>A striking difference in the kinetics of differential gene expression among our RM groups suggests that <jats:italic>Mamu-B*08<\/jats:italic>-associated elite control is characterized by a robust, rapid innate immune response that quickly resolves. These findings indicate that, despite the association between MHC class I genotype and elite control, innate immune factors in hyperacute SIV infection preceding CTL response development may facilitate the establishment of the EC phenotype.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1478063","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T04:30:58Z","timestamp":1729571458000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Acute-phase innate immune responses in SIVmac239-infected Mamu-B*08+ Indian rhesus macaques may contribute to the establishment of elite control"],"prefix":"10.3389","volume":"15","author":[{"given":"Brandon 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