Identification of constitutive NK cell features associated with post-treatment control of SIV infection. The pVISCONTI study

Identification of constitutive NK cell features associated with post-treatment control of SIV infection. The pVISCONTI study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Identification of constitutive NK cell features associated with post-treatment control of SIV infection. The pVISCONTI study Asier Saez-Cirion, Anais Chapel, Luis Romero-Martin, Caroline Passaes, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8789706/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Post-treatment HIV controllers (PTC) offer a unique opportunity to uncover the determinants of durable remission after antiretroviral therapy (ART) interruption. Early ART initiation has been shown to favor this outcome, but the underlying immune mechanisms remain unclear. Recent reports suggest that natural killer (NK) cells may play a key role in post-treatment control of infection; however, a direct association with specific NK cell features has not been firmly established. We used a recently reported model of post-treatment control of SIVmac251 infection in Cynomolgus macaques (the pVISCONTI study) to analyze the constitutive and infection-induced characteristics of NK cells and their association with post-treatment viral control. Studying six PTC and six post-treatment non-controllers, we identified two NK cell subsets differing in the expression of NKG2A, NKp30, and NKp46, and which abundance prior to infection showed opposite associations with the outcome after ART interruption. NKG2Ahigh NK cells lacking NKp30/NKp46 (NKG2AhighNKp30-NKp46-), shaped by the MHC background of the animals, were linked to improved post-treatment control. This subset displayed tissue-homing potential and preserved functionality despite infection, characterized by cytokine production and degranulation. Conversely, NKG2AlowNKp30+NKp46+ NK cells exhibited reduced cytotoxicity and elevated IL-10/IL-17A production, and their pre-infection levels were associated with higher viremia and larger viral reservoirs after ART interruption. Our study indicates that constitutive NK cell features, preserved by early ART initiation, may provide a favorable immune environment for post-treatment control. These findings further identify the NKG2A axis as a potential target to improve outcomes after ART interruption. Health sciences/Diseases/Infectious diseases/HIV infections Biological sciences/Immunology/Infectious diseases/HIV infections Biological sciences/Immunology/Innate immune cells/Innate lymphoid cells Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Early ART initiation has been shown to favor this outcome, but the underlying immune mechanisms remain unclear. Recent reports suggest that natural killer (NK) cells may play a key role in post-treatment control of infection; however, a direct association with specific NK cell features has not been firmly established. \r\n\r\nWe used a recently reported model of post-treatment control of SIVmac251 infection in Cynomolgus macaques (the pVISCONTI study) to analyze the constitutive and infection-induced characteristics of NK cells and their association with post-treatment viral control. Studying six PTC and six post-treatment non-controllers, we identified two NK cell subsets differing in the expression of NKG2A, NKp30, and NKp46, and which abundance prior to infection showed opposite associations with the outcome after ART interruption. NKG2Ahigh NK cells lacking NKp30/NKp46 (NKG2AhighNKp30-NKp46-), shaped by the MHC background of the animals, were linked to improved post-treatment control. This subset displayed tissue-homing potential and preserved functionality despite infection, characterized by cytokine production and degranulation. Conversely, NKG2AlowNKp30+NKp46+ NK cells exhibited reduced cytotoxicity and elevated IL-10/IL-17A production, and their pre-infection levels were associated with higher viremia and larger viral reservoirs after ART interruption. \r\n\r\nOur study indicates that constitutive NK cell features, preserved by early ART initiation, may provide a favorable immune environment for post-treatment control. These findings further identify the NKG2A axis as a potential target to improve outcomes after ART interruption.","manuscriptTitle":"Identification of constitutive NK cell features associated with post-treatment control of SIV infection. 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