Norovirus immunology: Of mice and mechanisms

• Type of Material: Article
• Authors: Kira L. Newman, Emory University; Juan Leon, Emory University
• Language: English
• Date: 2015-10-01
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
• Final Published Version (URL): http://dx.doi.org/10.1002/eji.201545512
• Title of Journal or Parent Work: EUROPEAN JOURNAL OF IMMUNOLOGY
• Volume: 45
• Issue: 10
• Start Page: 2742
• End Page: 2757
• Grant/Funding Information: This work was supported by the F30 grant (K.L.N., grant 1F30DK100097), the ARCS Foundation (K.L.N), the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (J.S.L., grant 1K01AI087724-01), and U.S. Department of Agriculture, National Institute of Food and Agriculture (J.S.L. grant 2015-67017-23080).
• Keywords: Science & Technology; CELLULAR IMMUNE-RESPONSES; Norovirus; Vaccine; PORCINE ENTERIC CALICIVIRUS; POSTNATAL-DEVELOPMENT; Life Sciences & Biomedicine; BLOOD GROUP ANTIGENS; Immunology; Human; INFECTIOUS NONBACTERIAL GASTROENTERITIS; ATTACHMENT RECEPTORS; SNOW-MOUNTAIN; HAWAII AGENT; Animal models; UNITED-STATES; Microbiome; NORWALK VIRUS-INFECTION
• Research Categories: Biology, Virology; Health Sciences, Immunology

Abstract

Noroviruses (NoVs) are the most common cause of sporadic and epidemic gastroenteritis in the United States and Europe and are responsible for 20% of acute gastroenteritis worldwide. Over the past decade, the understanding of NoV immunology has grown immensely. Studies of the natural immune response to NoV in humans and animal models have laid the foundation for innovations in cell culture systems for NoV and development of new therapeutics. Evidence from animal models, NoV surrogates, observational human research, and human challenge studies suggest that the innate immune response is critical for limiting NoV infection but is insufficient for viral clearance. NoV may antagonize the innate immune response to establish or prolong infection. However, once a robust adaptive immune response is initiated, the immune system clears the infection through the action of T and B cells, simultaneously generating highly specific protective immunologic memory. We review here both the current knowledge on NoV immunity and exciting new developments, with a focus on ongoing vaccine development work, novel cell culture systems, and advances in understanding the role of the gut microbiome. These changes reinforce the need for a better understanding of the human immune response to NoV and suggest novel hypotheses.