Japanese encephalitis virus and its mechanisms of neuroinvasion

• Published in: PLoS pathogens Vol. 16; no. 4; p. e1008260
• Main Authors: Hsieh, Justin T, St John, Ashley L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2020; Public Library of Science (PLoS)
• Subjects: Biology and Life Sciences; Blood-brain barrier; Central nervous system; Cerebrospinal fluid; Chymase; Encephalitis; Endothelial cells; Global health; Health care facilities; Immune system; Immunology; Infections; Infectious diseases; Invasiveness; Japanese encephalitis; Lymphocytes; Malware; Matrix metalloproteinase; Matrix metalloproteinases; Medicine and Health Sciences; Metalloproteinase; Microbiology; Morbidity; Mortality; Mosquitoes; Myeloid cells; Nervous system; Neurophysiology; Parenchyma; Pearls; Peripheral nervous system; Permeability; Proteins; Reactive oxygen species; Retrograde transport; RNA; RNA viruses; Swine; Tight junctions; Translocation; Vaccines; Vector-borne diseases; Viral encephalitis; Viruses; Japan; Singapore
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1008260

About the Authors: Justin T. Hsieh Affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore ORCID logo http://orcid.org/0000-0002-9701-0998 Ashley L. St. John * E-mail: ashley.st.john@duke-nus.edu.sg Affiliations Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingHealth Duke-NUS Global Health Institute, Singapore, Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America ORCID logo http://orcid.org/0000-0001-5098-1044 Introduction Japanese encephalitis virus (JEV) is a positive-sense single-stranded RNA virus of the Flavivirus genus that is spread by Culex mosquitos. Neuroinvasive viruses use several mechanisms to access the CNS: (1) direct infection of endothelial cells and subsequent transcellular release of virus into the brain parenchyma, (2) infection of peripheral immune cells that enter the CNS in a “Trojan Horse” mechanism, (3) paracellular entry following breakdown of the BBB, (4) retrograde transport of virus from the peripheral nervous system (PNS) into the CNS, and (5) translocation from the blood to the cerebral spinal fluid (CSF) [5, 6] (Fig 1). In vivo, therapeutically inhibiting chymase reduced JEV penetration of the BBB and reduced the morbidity and mortality associated with JE [12]. [...]MCs facilitate paracellular entry of JEV across the BBB. BBB, blood–brain barrier; CNS, central nervous system; JEV, Japanese encephalitis virus; MC, mast cell; MMP, matrix metalloproteinase; ROS, reactive oxygen species; TJ, tight junctions. https://doi.org/10.1371/journal.ppat.1008260.g002 Other peripheral myeloid cells may contribute to neuroinvasion Another potential pathway establishing CNS infection is through infection of peripheral immune cells that can subsequently gain entry into the CNS in a “Trojan Horse” mechanism.