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Virulence Dec 2021Thousands of human deaths occur annually due to Japanese encephalitis (JE), caused by Japanese encephalitis virus. During the virus infection of the central nervous... (Review)
Review
Thousands of human deaths occur annually due to Japanese encephalitis (JE), caused by Japanese encephalitis virus. During the virus infection of the central nervous system, reactive gliosis, uncontrolled inflammatory response, and neuronal cell death are considered as the characteristic features of JE. To date, no specific treatment has been approved to overcome JE, indicating a need for the development of novel therapies. In this article, we focused on basic biological mechanisms in glial (microglia and astrocytes) and neuronal cells that contribute to the onset of neuroinflammation and neuronal cell damage during Japanese encephalitis virus infection. We also provided comprehensive knowledge about anti-JE therapies tested in clinical or pre-clinical settings, and discussed recent therapeutic strategies that could be employed for JE treatment. The improved understanding of JE pathogenesis might lay a foundation for the development of novel therapies to halt JE. AKT: a serine/threonine-specific protein kinase; AP1: activator protein 1; ASC: apoptosis-associated speck-like protein containing a CARD; ASK1: apoptosis signal-regulated kinase 1; ATF3/4/6: activating transcription factor 3/4/6; ATG5/7: autophagy-related 5/7; BBB: blood-brain barrier; Bcl-3/6: B-cell lymphoma 3/6 protein; CCL: C-C motif chemokine ligand; CCR2: C-C motif chemokine receptor 2; CHOP: C/EBP homologous protein; circRNA: circular RNA; CNS: central nervous system; CXCL: C-X-C motif chemokine ligand; dsRNA: double-stranded RNA; EDEM1: endoplasmic reticulum degradation enhancer mannosidase alpha-like 1; eIF2-ɑ: eukaryotic initiation factor 2 alpha; ER: endoplasmic reticulum; ERK: extracellular signal-regulated kinase; GRP78: 78-kDa glucose-regulated protein; ICAM: intercellular adhesion molecule; IFN: interferon; IL: interleukin; iNOS: inducible nitric oxide synthase; IRAK1/2: interleukin-1 receptor-associated kinase 1/2; IRE-1: inositol-requiring enzyme 1; IRF: interferon regulatory factor; ISG15: interferon-stimulated gene 15; JE: Japanese encephalitis; JEV: Japanese encephalitis virus; JNK: c-Jun N-terminal kinase; LAMP2: lysosome-associated membrane protein type 2; LC3-I/II: microtubule-associated protein 1 light chain 3-I/II; lncRNA: long non-coding RNA; MAPK: mitogen-activated protein kinase; miR/miRNA: microRNA; MK2: mitogen-activated protein kinase-activated protein kinase 2; MKK4: mitogen-activated protein kinase kinase 4; MLKL: mixed-linage kinase domain-like protein; MMP: matrix metalloproteinase; MyD88: myeloid differentiation factor 88; Nedd4: neural precursor cell-expressed developmentally downregulated 4; NF-κB: nuclear factor kappa B; NKRF: nuclear factor kappa B repressing factor; NLRP3: NLR family pyrin domain containing 3; NMDAR: N-methyl-D-aspartate receptor; NO: nitric oxide; NS2B/3/4: JEV non-structural protein 2B/3/4; P: phosphorylation. p38: mitogen-activated protein kinase p38; PKA: protein kinase A; PAK4: p21-activated kinase 4; PDFGR: platelet-derived growth factor receptor; PERK: protein kinase R-like endoplasmic reticulum kinase; PI3K: phosphoinositide 3-kinase; PTEN: phosphatase and tensin homolog; Rab7: Ras-related GTPase 7; Raf: proto-oncogene tyrosine-protein kinase Raf; Ras: a GTPase; RIDD: regulated IRE-1-dependent decay; RIG-I: retinoic acid-inducible gene I; RIPK1/3: receptor-interacting protein kinase 1/3; RNF11/125: RING finger protein 11/125; ROS: reactive oxygen species; SHIP1: SH2-containing inositol 5' phosphatase 1; SOCS5: suppressor of cytokine signaling 5; Src: proto-oncogene tyrosine-protein kinase Src; ssRNA = single-stranded RNA; STAT: signal transducer and activator of transcription; TLR: toll-like receptor; TNFAIP3: tumor necrosis factor alpha-induced protein 3; TNFAR: tumor necrosis factor alpha receptor; TNF-α: tumor necrosis factor-alpha; TRAF6: tumor necrosis factor receptor-associated factor 6; TRIF: TIR-domain-containing adapter-inducing interferon-β; TRIM25: tripartite motif-containing 25; VCAM: vascular cell adhesion molecule; ZO-1: zonula occludens-1.
Topics: Animals; Apoptosis; Cell Death; Encephalitis Virus, Japanese; Encephalitis, Japanese; Endoplasmic Reticulum Chaperone BiP; Humans; Inflammation; Mice; Nervous System Diseases; Neurons; Proto-Oncogene Mas; Signal Transduction; Virulence
PubMed: 33724154
DOI: 10.1080/21505594.2021.1899674 -
The American Journal of Tropical... May 2023Japanese encephalitis (JE) is becoming an increasingly important issue among adults. The reasons for this are multifactorial. During the past decades, new areas of... (Review)
Review
Japanese encephalitis (JE) is becoming an increasingly important issue among adults. The reasons for this are multifactorial. During the past decades, new areas of Japanese encephalitis virus (JEV) transmission have occurred in several locations, most notably in a markedly expanded area of Australia during 2021-2022. When JEV enters new areas, cases in adults frequently occur. This is unlike the typical pattern in endemic areas where the burden of disease is in children because most adults are protected through natural immunity following earlier exposure to the virus. Even in endemic areas, JEV has become relatively more important in adults because improved JE control through childhood immunization programs has resulted in a substantial decrease in pediatric JE cases and thus more prominence of adult JE cases. Finally, increases in tourism to JE risk areas have resulted in more exposure of adult travelers, who are usually non-immune, to infection in JE risk areas. In this review we describe the increasing importance of JE in adults in some areas and then consider the comparative clinical presentation and severity of illness among children and adults.
Topics: Adult; Child; Humans; Encephalitis, Japanese; Encephalitis Virus, Japanese; Australia; Immunity, Innate; Immunization Programs; Japanese Encephalitis Vaccines
PubMed: 37037440
DOI: 10.4269/ajtmh.23-0036 -
Virus Research Jul 2023Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic virus that can cause severe viral encephalitis. Initial interactions between JEV and host cells are... (Review)
Review
Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic virus that can cause severe viral encephalitis. Initial interactions between JEV and host cells are required for productive viral infection and initiation of the viral life cycle. The elucidation of these interactions is critical, not only to understand the pathogenesis of JEV infection, but also to design efficient antiviral strategies. In this review, we outline the known viral and cellular components involved in JEV entry into host cells, with a particular focus on the initial virus-host cell interaction on the cell surface and the downstream early events such as endocytosis, membrane fusion, and viral genome release.
Topics: Animals; Humans; Encephalitis Virus, Japanese; Host Microbial Interactions; Virus Internalization; Encephalitis, Japanese; Endocytosis; Encephalitis Viruses, Japanese; Virus Replication
PubMed: 37086856
DOI: 10.1016/j.virusres.2023.199120 -
Rhode Island Medical Journal (2013) Aug 2020Travelers to 24 endemic countries in Asia may be at risk for Japanese encephalitis. The ACIP has recently expanded guidelines on the use of Ixiaro, the inactivated... (Review)
Review
Travelers to 24 endemic countries in Asia may be at risk for Japanese encephalitis. The ACIP has recently expanded guidelines on the use of Ixiaro, the inactivated Japanese encephalitis vaccine. This article reviews the disease burden of Japanese encephalitis and the role of a travel clinic in guiding travelers to Asia regarding decision-making about the use of this highly protective vaccine.
Topics: Adolescent; Adult; Asia; Child; Child, Preschool; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans; Infant; Japanese Encephalitis Vaccines; Risk; Seasons; Travel
PubMed: 32752568
DOI: No ID Found -
Revue Scientifique Et Technique... Aug 2015Japanese encephalitis (JE) is an inflammation of the central nervous system in humans and animals, specifically horses and cattle. The disease, which can sometimes be...
Japanese encephalitis (JE) is an inflammation of the central nervous system in humans and animals, specifically horses and cattle. The disease, which can sometimes be fatal, is caused by the flavivirus Japanese encephalitis virus (JEV), of which there are five genotypes (genotypes 1, 2, 3, 4 and 5). The transmission cycle of the virus involves pigs and wild birds as virus amplifiers and mosquitoes as vectors for transferring the virus between amplifying hosts and to dead- end hosts, i.e. humans, horses and cattle. In horses and cattle the disease is usually asymptomatic, but when clinical signs do occur they include fever, decreased appetite, frothing at the mouth, rigidity of the legs and recumbency, and neurological signs, such as convulsive fits, circling, marked depression and disordered consciousness. In pigs, it can cause abortion and stillbirths. At present, the virus is detected in a wide area covering eastern and southern Asia, Indonesia, northern Australia, Papua New Guinea and Pakistan. JEV RNA has also been detected in Italy, first in dead birds in 1997 and 2000 and then in mosquitoes in 2010. Genotype shift, i.e. a change of genotype from genotype 3 to genotype 1, has occurred in some countries, namely Japan, South Korea, Chinese Taipei and Vietnam. Laboratory methods are available for confirming the causative agent of the disease. There are control measures to prevent or minimise infection and, among them, vaccination is one of the most important and one which should be adopted in endemic and epidemic areas.
Topics: Animals; Culex; Encephalitis Virus, Japanese; Encephalitis, Japanese; Genome, Viral; Humans; Insect Vectors; Zoonoses
PubMed: 26601447
DOI: 10.20506/rst.34.2.2370 -
CMAJ : Canadian Medical Association... May 2018
Topics: Encephalitis Virus, Japanese; Encephalitis, Japanese; Fatal Outcome; Fever; Headache; Humans; Immunoglobulins, Intravenous; Magnetic Resonance Imaging; Male; Middle Aged; Real-Time Polymerase Chain Reaction
PubMed: 29807939
DOI: 10.1503/cmaj.171341 -
Acta Tropica Sep 2018Japanese encephalitis (JE) is a vector-borne zoonotic disease caused by the Japanese encephalitis virus (JEV). It causes encephalitis in human and horses, and may lead... (Review)
Review
Japanese encephalitis (JE) is a vector-borne zoonotic disease caused by the Japanese encephalitis virus (JEV). It causes encephalitis in human and horses, and may lead to reproductive failure in sows. The first human encephalitis case in Malaya (now Malaysia) was reported during World War II in a British prison in 1942. Later, encephalitis was observed among race horses in Singapore. In 1951, the first JEV was isolated from the brain of an encephalitis patient. The true storyline of JE exposure among humans and animals has not been documented in Malaysia. In some places such as Sarawak, JEV has been isolated from mosquitoes before an outbreak in 1992. JE is an epidemic in Malaysia except Sarawak. There are four major outbreaks reported in Pulau Langkawi (1974), Penang (1988), Perak and Negeri Sembilan (1998-1999), and Sarawak (1992). JE is considered endemic only in Sarawak. Initially, both adults and children were victims of JE in Malaysia, however, according to the current reports; JE infection is only lethal to children in Malaysia. This paper describes a timeline of JE cases (background of each case) from first detection to current status, vaccination programs against JE, diagnostic methods used in hospitals and factors which may contribute to the transmission of JE among humans and animals in Malaysia.
Topics: Animals; Disease Outbreaks; Encephalitis, Japanese; Humans; Japanese Encephalitis Vaccines; Malaysia; Vaccination
PubMed: 29856986
DOI: 10.1016/j.actatropica.2018.05.017 -
Human Vaccines & Immunotherapeutics Nov 2021Japanese encephalitis (JE) is an endemic disease dominantly in the Asia-Pacific region with mortality rate varying between 3% and 30%. Long-term neuropsychiatric...
Japanese encephalitis (JE) is an endemic disease dominantly in the Asia-Pacific region with mortality rate varying between 3% and 30%. Long-term neuropsychiatric sequelae developed in 30-50% of the survivors. There is no available antiviral therapy for JE. JE vaccines play a major role in preventing this devastating disease. The incidence of JE declined over years and the age distribution shifted toward adults in countries where JE immunization program exists. Mouse brain-JE vaccine is currently replaced by inactivated Vero cell-derived vaccine and live-attenuated vaccine using SA14-14-2 strain, and live chimeric JE vaccines. These three types of JE vaccines are associated with favorable efficacy and safety profiles. Common adverse reactions include injection site reactions and fever, and severe adverse reactions are rare.
Topics: Animals; Chlorocebus aethiops; Encephalitis Virus, Japanese; Encephalitis, Japanese; Japanese Encephalitis Vaccines; Mice; Vaccines, Attenuated; Vaccines, Inactivated; Vero Cells
PubMed: 34613870
DOI: 10.1080/21645515.2021.1969852 -
Journal of Biomedical Science Jun 2021Dysregulated formation of neutrophil extracellular traps (NETs) is observed in acute viral infections. Moreover, NETs contribute to the pathogenesis of acute viral... (Review)
Review
Dysregulated formation of neutrophil extracellular traps (NETs) is observed in acute viral infections. Moreover, NETs contribute to the pathogenesis of acute viral infections, including those caused by the dengue virus (DV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Furthermore, excessive NET formation (NETosis) is associated with disease severity in patients suffering from SARS-CoV-2-induced multiple organ injuries. Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and other members of C-type lectin family (L-SIGN, LSECtin, CLEC10A) have been reported to interact with viral glycans to facilitate virus spreading and exacerbates inflammatory reactions. Moreover, spleen tyrosine kinase (Syk)-coupled C-type lectin member 5A (CLEC5A) has been shown as the pattern recognition receptor for members of flaviviruses, and is responsible for DV-induced cytokine storm and Japanese encephalomyelitis virus (JEV)-induced neuronal inflammation. Moreover, DV activates platelets via CLEC2 to release extracellular vesicles (EVs), including microvesicles (MVs) and exosomes (EXOs). The DV-activated EXOs (DV-EXOs) and MVs (DV-MVs) stimulate CLEC5A and Toll-like receptor 2 (TLR2), respectively, to enhance NET formation and inflammatory reactions. Thus, EVs from virus-activated platelets (PLT-EVs) are potent endogenous danger signals, and blockade of C-type lectins is a promising strategy to attenuate virus-induced NETosis and intravascular coagulopathy.
Topics: Blood Platelets; COVID-19; Cytokine Release Syndrome; Encephalitis Virus, Japanese; Encephalitis, Japanese; Extracellular Traps; Humans; Lectins, C-Type; Platelet Activation; SARS-CoV-2; Signal Transduction
PubMed: 34116654
DOI: 10.1186/s12929-021-00741-7 -
Human Vaccines & Immunotherapeutics Jan 2018Japanese encephalitis (JE) is the most commonly diagnosed viral encephalitis in Asia. JE is caused by a virus called JE virus (JEV), a member of the genus Flavivirus,... (Review)
Review
Japanese encephalitis (JE) is the most commonly diagnosed viral encephalitis in Asia. JE is caused by a virus called JE virus (JEV), a member of the genus Flavivirus, family Flaviviridae, and is transmitted by Culex mosquitoes. Neutralising antibody to JEV protects against JE, and can be induced by vaccination. JE is a potential threat to travellers to endemic areas, which are most of South and Southeast Asia and some Pacific Islands. The risk of JE can be expected to increase with increasing mosquito exposure and time spent in regions and seasons of active transmission. JE is very rare in travellers, but mortality is high, around 1 in 3, and there is a high rate of lasting neurological damage. JE can therefore be a profoundly life changing event for a traveller. Travellers and their healthcare providers need to balance the low risk of disease against the very high severity of disease if it does occur. In order to make an informed decision, the severity of JE disease should be carefully explained to travellers to Asia.
Topics: Asia; Decision Making; Encephalitis Virus, Japanese; Encephalitis, Japanese; Endemic Diseases; Humans; Japanese Encephalitis Vaccines; Risk Assessment; Seasons; Severity of Illness Index; Travel-Related Illness; Vaccination
PubMed: 29244615
DOI: 10.1080/21645515.2017.1380756