Regulation of inflammation in Japanese encephalitis

Lannes, Nils; Summerfield, Artur; Filgueira, Luis

doi:10.1186/s12974-017-0931-5

Cited by 67 publications

(69 citation statements)

References 105 publications

(317 reference statements)

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“…In humans, JEV has been found in different anatomical compartments and a variety of cell types is able to support its replication. These include endothelial cells, granulocytes, dendritic cells, macrophages and cells of the CNS including astrocytes, neurons and microglia ( 92 ). The virus spreads from dermal tissues ( 93 ) to lymphoid organs ( 94 ) and during the acute stage of infection can be found in blood ( 95 ).…”

Section: Japanese Encephalitis Virusmentioning

confidence: 99%

Flavivirus Receptors: Diversity, Identity, and Cell Entry

et al. 2018

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Flaviviruses are emerging and re-emerging arthropod-borne pathogens responsible for significant mortality and morbidity worldwide. The genus comprises more than seventy small, positive-sense, single-stranded RNA viruses, which are responsible for a spectrum of human and animal diseases ranging in symptoms from mild, influenza-like infection to fatal encephalitis and haemorrhagic fever. Despite genomic and structural similarities across the genus, infections by different flaviviruses result in disparate clinical presentations. This review focusses on two haemorrhagic flaviviruses, dengue virus and yellow fever virus, and two neurotropic flaviviruses, Japanese encephalitis virus and Zika virus. We review current knowledge on host-pathogen interactions, virus entry strategies and tropism.

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Section: Japanese Encephalitis Virusmentioning

confidence: 99%

Flavivirus Receptors: Diversity, Identity, and Cell Entry

et al. 2018

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“…Once present in the CNS, inflammation due to JEV amplifies BBB breakdown. Pericytes, which are situated within the basement membrane next to endothelial cells, aid in breakdown of the BBB through release of IL-6, which leads to ZO-1 degradation [17]. Coculture of astrocytes and brain endothelial cells increases TJ leakiness through increased release of mediators such as IL-6, CCL5, and CXCL10 [17] (Fig 2).…”

Section: Amplification Of Bbb Leakiness By Jev Infection Within the Bmentioning

confidence: 99%

“…Pericytes, which are situated within the basement membrane next to endothelial cells, aid in breakdown of the BBB through release of IL-6, which leads to ZO-1 degradation [17]. Coculture of astrocytes and brain endothelial cells increases TJ leakiness through increased release of mediators such as IL-6, CCL5, and CXCL10 [17] (Fig 2). Microglia also release proinflammatory mediators such as TNF-α to promote BBB leakiness [17].…”

Section: Amplification Of Bbb Leakiness By Jev Infection Within the Bmentioning

confidence: 99%

“…Coculture of astrocytes and brain endothelial cells increases TJ leakiness through increased release of mediators such as IL-6, CCL5, and CXCL10 [17] (Fig 2). Microglia also release proinflammatory mediators such as TNF-α to promote BBB leakiness [17]. At the latter stages of disease, CNS supporting cells are activated and accentuate BBB leakiness and disease, but this increased permeability may also allow penetration of immune cells that are necessary for infection clearance, such as T cells [18].…”

Section: Amplification Of Bbb Leakiness By Jev Infection Within the Bmentioning

confidence: 99%

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Japanese encephalitis virus and its mechanisms of neuroinvasion

Hsieh

John

2020

PLoS Pathog

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Japanese encephalitis virus (JEV) is a positive-sense single-stranded RNA virus of the Flavivirus genus that is spread by Culex mosquitos. It is maintained in an enzootic cycle in pigs and wild birds in which humans are dead-end hosts [1]. Despite having effective vaccines, JEV is the leading cause of viral encephalitis in Asia [1]. As a neuroinvasive virus, it can effectively cross the blood-brain barrier (BBB) to cause acute encephalitis. Twenty-five percent to 30% of Japanese encephalitis (JE) cases are fatal, and 50% result in permanent neuropsychiatric complications [2]. There are currently no treatments for JE, partly due to an incomplete understanding of the mechanisms promoting encephalitis. The central nervous system (CNS) relies on the BBB, a tightly regulated barrier between the peripheral circulation and the CNS, to prevent entry of pathogens, including viruses. Yet, JEV and other neuroinvasive viruses can overcome the BBB, which usually excludes foreign substances. It is formed primarily by tight junctions (TJ) between endothelial cells, comprised of proteins such as claudin-5, zonula occludens (ZO)-1, and occludin. The BBB is sustained by supporting cell types, including astrocytes, pericytes, microglia, and mast cells (MCs) [1, 3]. Together, these cells form neurovascular units that maintain a barrier along the cerebrovascular microvessels to promote immune privilege and CNS homeostasis [3, 4]. 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). JEV infection through the natural subcutaneous route leads to widespread infection in various parts of the brain [7], suggesting a hematological route of infection, such as would occur for mechanisms 1-3. Here we provide an overview of a few described mechanisms of JEV penetration of the BBB and processes that amplify CNS infection. Transcellular infection of endothelial cells and activation of the neurovascular unit Some neurotropic viruses directly infect endothelial cells to reach the brain from the circulation and travel transcellularly to release viruses into the brain parenchyma [6]. JEV has been

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“…Japanese encephalitis virus (JEV) is a positive-sense, single-stranded RNA virus belonging to the genus Flavivirus in the family Flaviviridae. JEV is both neurovirulent and neuroinvasive and can lead to severe encephalitis (Lannes et al, 2017). Glycoprotein E mediates JEV entry through attachment and endocytosis, followed by membrane fusion and uncoating (Wang et al, 2017;Yun and Lee, 2018).…”

Section: Introductionmentioning

confidence: 99%

RIPK3 Promotes JEV Replication in Neurons via Downregulation of IFI44L

Bian

Zheng

et al. 2020

Front. Microbiol.

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Japanese encephalitis virus (JEV), the leading cause of viral encephalitis in Asia, is neurovirulent and neuroinvasive. Neurons are the main target of JEV infection and propagation. Receptor interacting serine/threonine-protein kinase 3 (RIPK3) has been reported to contribute to neuroinflammation and neuronal death in many central nervous system diseases. In this study, we found that the progression of JE was alleviated in RIPK3-knockout (RIPK3 −/− ) mice in both peripheral and intracerebral infection. RIPK3knockdown (RIPK3-RNAi) neuro2a cells showed higher cell viability during JEV infection. Moreover, the JEV load was significantly decreased in RIPK3 −/− mouse-derived primary neurons and RIPK3-RNAi neuro2a cells compared with wild-type neurons, but this was not observed in microglia. Furthermore, RNA sequencing of brain tissues showed that the level of the interferon (IFN)-induced protein 44-like gene (IFI44L) was significantly increased in JEV-infected RIPK3 −/− mouse brains, RIPK3 −/− neurons, and RIPK3-RNAi-neuro2a cells. Then, it was demonstrated that the propagation of JEV was inhibited in IFI44L-overexpressing neuro2a cells and enhanced in IFI44L and RIPK3 double knockdown neuro2a cells. Taken together, our results showed that the increased expression of RIPK3 following JEV infection played complicated roles. On the one hand, RIPK3 participated in neuroinflammation and neuronal death during JEV infection. On the other hand, RIPK3 inhibited the expression of IFI44L to some extent, leading to the propagation of JEV in neurons, which might be a strategy for JEV to evade the cellular innate immune response. Keywords: Japanese encephalitis virus (JEV), receptor interacting serine/threonine-protein kinase 3 (RIPK3), interferon-induced protein 44-like gene (IFI44L), neurons, cellular innate immune response Frontiers in Microbiology | www.frontiersin.org March 2020 | Volume 11 | Article 368 Frontiers in Microbiology | www.frontiersin.org

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Regulation of inflammation in Japanese encephalitis

Cited by 67 publications

References 105 publications

Flavivirus Receptors: Diversity, Identity, and Cell Entry

Flavivirus Receptors: Diversity, Identity, and Cell Entry

Japanese encephalitis virus and its mechanisms of neuroinvasion

RIPK3 Promotes JEV Replication in Neurons via Downregulation of IFI44L

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