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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 -
F1000Research 2020Encephalitis is an important cause of morbidity, mortality, and permanent neurologic sequelae globally. Causes are diverse and include viral and non-viral infections... (Review)
Review
Encephalitis is an important cause of morbidity, mortality, and permanent neurologic sequelae globally. Causes are diverse and include viral and non-viral infections of the brain as well as autoimmune processes. In the West, the autoimmune encephalitides are now more common than any single infectious cause, but, in Asia, infectious causes are still more common. In 2006, the World Health Organization coined the term "acute encephalitis syndrome", which simply means acute onset of fever with convulsions or altered consciousness or both. In 2013, the International Encephalitis Consortium set criteria for diagnosis of encephalitis on basis of clinical and laboratory features. The most important infectious cause in the West is herpes simplex virus, but globally Japanese encephalitis (JE) remains the single largest cause. Etiologic diagnosis is difficult because of the large number of agents that can cause encephalitis. Also, the responsible virus may be detectable only in the brain and is either absent or transiently found in blood or cerebrospinal fluid (CSF). Virological diagnosis is complex, expensive, and time-consuming. Different centres could make their own algorithms for investigation in accordance with the local etiologic scenarios. Magnetic resonance imaging (MRI) and electroencephalography are specific for few agents. Clinically, severity may vary widely. A severe case may manifest with fever, convulsions, coma, neurologic deficits, and death. Autoimmune encephalitis (AIE) includes two major categories: (i) classic paraneoplastic limbic encephalitis (LE) with autoantibodies against intracellular neuronal antigens (Eg: Hu and Ma2) and (ii) new-type AIE with autoantibodies to neuronal surface or synaptic antigens (Eg: anti-N-methyl-D-aspartate receptor). AIE has prominent psychiatric manifestations: psychosis, aggression, mutism, memory loss, euphoria, or fear. Seizures, cognitive decline, coma, and abnormal movements are common. Symptoms may fluctuate rapidly. Treatment is largely supportive. Specific treatment is available for herpesvirus group and non-viral infections. Various forms of immunotherapy are used for AIE.
Topics: Acute Disease; Animals; Autoantibodies; Encephalitis; Hashimoto Disease; Humans; Receptors, N-Methyl-D-Aspartate
PubMed: 32047620
DOI: 10.12688/f1000research.20634.1 -
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 -
Current Treatment Options in Infectious... 2020As an eminently vaccine-preventable disease, encephalitis caused by Japanese encephalitis virus (JEV) has attracted an unusually high degree of attention from those... (Review)
Review
PURPOSE OF REVIEW
As an eminently vaccine-preventable disease, encephalitis caused by Japanese encephalitis virus (JEV) has attracted an unusually high degree of attention from those seeking to develop viral vaccines. Since the 1950s, all types of JEV vaccines including inactivated, recombinant and live attenuated ones have been licensed. As an example of an extremely successful endeavour, the time is ripe for reviewing the development of JEV vaccines and probing the reasons behind their uniform success.
RECENT FINDINGS
Vaccines against JEV have come a long way since the first licensing in the mid-1950s of the mouse brain-grown-inactivated virus preparations, to the present day live-attenuated virus vaccines. A survey of the various inactivated and live vaccines developed against JEV provides a striking insight into the impressive safety and efficacy of all the vaccines available to prevent encephalitis from JEV. This review juxtaposes studies to understand naturally acquired immunity against JEV that have mostly been published post-2000, compares these with those elicited by vaccines and highlights the paucity of data on cell-mediated immune responses elicited by JEV vaccines.
SUMMARY
This article not only seeks to make available the immense salient literature on this endeavour in one collection, but also queries the basis for the remarkable success of JEV vaccines, not least of which may be the ease of protecting against encephalitis caused by JEV. To conclude, the true test of the ingenuity of those dedicated to the pursuit of viral vaccines would be success against viral diseases such as HIV-AIDS and dengue that pose a far greater challenge to scientists.
PubMed: 33204220
DOI: 10.1007/s40506-020-00242-5 -
Pathogens (Basel, Switzerland) Dec 2023Flaviviruses are a group of positive-sense, single-stranded RNA viruses predominantly transmitted by arthropods (mainly mosquitoes) that cause severe endemic infections... (Review)
Review
Flaviviruses are a group of positive-sense, single-stranded RNA viruses predominantly transmitted by arthropods (mainly mosquitoes) that cause severe endemic infections and epidemics on a global scale. They represent a major cause of systemic morbidity and death and are expanding worldwide. Among this group, dengue fever, the West Nile virus, yellow fever, Japanese Encephalitis, and, recently, the Zika virus have been linked to a spectrum of ocular manifestations. These manifestations encompass subconjunctival hemorrhages and conjunctivitis, anterior and posterior uveitis (inclusive of vitritis, chorioretinitis, and retinal vasculitis), maculopathy, retinal hemorrhages, and optic neuritis. Clinical diagnosis of these infectious diseases is primarily based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. Diagnosis confirmation relies on laboratory testing, including RT-PCR and serological testing. Ocular involvement typically follows a self-limited course but can result in irreversible visual impairment. Effective treatments of flavivirus infections are currently unavailable. Prevention remains the mainstay for arthropod vector and zoonotic disease control. Effective vaccines are available only for the yellow fever virus, dengue virus, and Japanese Encephalitis virus. This review comprehensively summarizes the current knowledge regarding the ophthalmic manifestations of the foremost flavivirus-associated human diseases.
PubMed: 38133340
DOI: 10.3390/pathogens12121457 -
Microorganisms Feb 2023Flaviviruses are a diverse group of enveloped RNA viruses that cause significant clinical manifestations in the pregnancy and postpartum periods. This review highlights... (Review)
Review
Flaviviruses are a diverse group of enveloped RNA viruses that cause significant clinical manifestations in the pregnancy and postpartum periods. This review highlights the epidemiology, pathophysiology, clinical features, diagnosis, and prevention of the key arthropod-borne flaviviruses of concern in pregnancy and the neonatal period-Zika, Dengue, Japanese encephalitis, West Nile, and Yellow fever viruses. Increased disease severity during pregnancy, risk of congenital malformations, and manifestations of postnatal infection vary widely amongst this virus family and may be quite marked. Laboratory confirmation of infection is complex, especially due to the reliance on serology for which flavivirus cross-reactivity challenges diagnostic specificity. As such, a thorough clinical history including relevant geographic exposures and prior vaccinations is paramount for accurate diagnosis. Novel vaccines are eagerly anticipated to ameliorate the impact of these flaviviruses, particularly neuroinvasive disease manifestations and congenital infection, with consideration of vaccine safety in pregnant women and children pivotal. Moving forward, the geographical spread of flaviviruses, as for other zoonoses, will be heavily influenced by climate change due to the potential expansion of vector and reservoir host habitats. Ongoing 'One Health' engagement across the human-animal-environment interface is critical to detect and responding to emergent flavivirus epidemics.
PubMed: 36838398
DOI: 10.3390/microorganisms11020433