Viral encephalitis is characterized by inflammation of the brain parenchyma caused by a variety of viruses, among which the Japanese encephalitis (JE) virus (JEV) is a typical representative arbovirus. Neuronal death, neuroinflammation, and breakdown of the blood brain barrier (BBB) constitute vicious circles of JE progression. Currently, there is no effective therapy to prevent this damage. Growth arrest specific gene 6 (GAS6) is a secreted growth factor that binds to the TYRO3, AXL, and MERTK (TAM) family of receptor tyrosine kinases and has been demonstrated to participate in neuroprotection and suppression of inflammation in many central nervous system (CNS) diseases which has great potential for JE intervention. In this study, we found that GAS6 expression in the brain was decreased and was reversely correlated with viral load and neuronal loss. Mice with GAS6/TAM signalling deficiency showed higher mortality and accelerated neuroinflammation during peripheral JEV infection, accompanied by BBB breakdown. GAS6 directly promoted the expression of tight junction proteins in bEnd.3 cells and strengthened BBB integrity, partly via AXL. Mice administered GAS6 were more resistant to JEV infection due to increased BBB integrity, as well as decreased viral load and neuroinflammation. Thus, targeted GAS6 delivery may represent a strategy for the prevention and treatment of JE especially in patients with impaired BBB.
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http://dx.doi.org/10.1186/s12974-024-03225-1 | DOI Listing |
Epidemiol Infect
December 2024
School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland, Australia.
In 2022, the largest ever virgin soil outbreak of Japanese encephalitis (JE) occurred in Australia resulting in 45 reported human cases of JE, with seven fatalities. Japanese encephalitis virus (JEV) was detected in 84 piggeries across Australia. In response, states implemented targeted vaccination programs for those individuals at the highest risk of JEV exposure.
View Article and Find Full Text PDFParasit Vectors
December 2024
Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, 41566, Republic of Korea.
Background: Culex tritaeniorhynchus, a major vector of Japanese encephalitis virus (JEV), is found across a broad geographical range, including Africa, Asia, Australia and Europe. Understanding the population structure and genetic diversity of pathogen vectors is increasingly seen as important for effective disease control. In China and Japan, two countries in close proximity to the Republic of Korea (ROK), Cx.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Animal-derived Food Safety Innovation Team, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Lab of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei 230036, China. Electronic address:
Japanese encephalitis caused by Japanese encephalitis virus (JEV) infection leads to the central nervous system disorder in human and swine. Viruses utilize the host protein synthesis mechanisms to efficiently translate their RNAs. Herein, we demonstrated that the host transcription factor SOX10 downregulated an RNA-binding protein heterogeneous nuclear ribonucleoprotein H (HNRNPH1) during JEV infection.
View Article and Find Full Text PDFOpen Forum Infect Dis
December 2024
Clinical Department, Children's Hospital 1, Ho Chi Minh City, Vietnam.
Background: The recognition of autoimmune causes of encephalitis has led to epidemiological shifts in the worldwide characteristics of encephalitis. -methyl-D-aspartate receptor (NMDAR) antibody encephalitis leads to well-established complex neuropsychiatric manifestations. In low- and middle-income countries, including Vietnam, its relative incidence, especially in children, is unknown and most neurologists currently consider infectious encephalitis prior to autoimmune etiologies.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
Japanese encephalitis virus (JEV) NS2B-NS3 is a protein complex composed of NS3 proteases and an NS2B co-factor. The N-terminal protease domain (180 residues) of NS3 (NS3(pro)) interacts directly with a central 40-amino acid hydrophilic domain of NS2B (NS2B(H)) to form an active serine protease. In this study, the recombinant NS2B(H)-NS3(pro) proteases were prepared in and used to compare the enzymatic activity between genotype I (GI) and III (GIII) NS2B-NS3 proteases.
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