A high-resolution, unbiased analysis of the cellular immune response to Epstein-Barr virus

A high-resolution, unbiased analysis of the cellular immune response to Epstein-Barr virus | 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 A high-resolution, unbiased analysis of the cellular immune response to Epstein-Barr virus Hugh Reyburn, Álvaro Fernando García Jiménez, Arianna Picozzi, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7887257/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract More than 95% of humans are infected with Epstein-Barr virus (EBV), yet although EBV infection has been associated with inflammatory and autoimmune diseases, lymphoproliferative disorders, and several types of cancer, for the vast majority of infected people the infection is asymptomatic as EBV replication is controlled by the immune system. Immunity against this virus has been studied since the discovery of EBV in the 1960s, and although important insights have been made, no unbiased, global studies of immune responses to EBV in healthy seropositive subjects have been reported. Here we describe a novel protocol to study the cellular immune response to EBV, detecting lymphocytes that respond to EBV via analyses of proliferation or induced expression of activation markers and cytokines. Using this system we sequenced, for the first time at a single-cell level, the transcriptome of all cells capable of responding to EBV in healthy individuals and in patients with inborn errors of immunity (IEI) associated with susceptibility to EBV infection. Lymphocyte cytotoxicity appears to be crucial for the proper control of EBV-infection, while a proportionate T-regulatory cell response likely helps to avoid excessive immunity and immune pathology. We also show that γδ T cells expressing the TCR Vδ1 chain use various activating natural killer (NK) cell receptors to recognise and kill EBV-infected lymphoblastoid cell lines (LCLs) and thus could be a promising candidate for allogeneic cell therapy for EBV-associated lymphoproliferative disorders in patients with either primary or secondary immunodeficiencies. Health sciences/Pathogenesis/Infection Biological sciences/Immunology/Infectious diseases/Viral infection Epstein-Barr virus Inborn Errors of Immunity scRNA-seq Vδ1 cells Full Text Additional Declarations There is NO Competing Interest. Supplementary Files GarciaJimenezetalsupplementary.pdf Supplementary information Cite Share Download PDF Status: Posted 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. 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