Japanese Encephalitis Virus Activates Autophagy as a Viral Immune Evasion Strategy

Jin, Rui; Zhu, Wandi; Cao, Shengbo; Chen, Rui; Jin, Hui; Liu, Yang; Wang, Shaobo; Wang, Wei; Xiao, Gengfu

doi:10.1371/journal.pone.0052909

Cited by 77 publications

(75 citation statements)

References 45 publications

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“…In contrast to dengue virus, the autophagic vacuole shows no evidence of being the site of replication for JEV. However, this finding is not consistent with the experiments conducted by Jin et al [48] and Wang et al [49] , who stated that the accumulation of the autophagosome and the autophagosome-lysosome fusion are essential to promote JEV replication [47][48][49] . In addition to initiating autophagy, viral intrusion also affects the intermediate step of the event.…”

Section: Autophagy Induction and Intracellular Replication In Viral Ccontrasting

confidence: 81%

Interactions between neurotropic pathogens, neuroinflammatory pathways, and autophagic neural cell death

Sahu¹,

Ter²

2018

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In recent times, there has been a significant increase in studies focusing on immunological functions of autophagy, however, knowledge of its roles and regulations in the central nervous system remains unclear. Present reviews highlight the molecular cross talk between host cell autophagy with inflammatory pathways in the context of neuro-infections. Intracellular pathogens might have an ability to manipulate the autophagy regulation process. An augmented autophagy and inflammation at the site of infection is traditionally considered host protective. Moreover, host cell autophagy might also facilitate pathogen survivability and multiplication in the brain environment. Consequently, an excessive autophagy and neuroinflammatory process do put surrounding healthy brain tissue at risk of pathogen invasion. The question arises, whether there are any known direct interactions of intracellular neurotropic pathogens with this degradative pathway that favour intracerebral pathogen survival and growth? It is worth exploring any such cooperation between pathogen factors and altered immune pathways that modulate autophagy regulatory genes causing massive neuronal damage. A detailed understanding of molecular mechanisms in microbial pathogenesis, neuroinflammatory and neuronal autophagy pathways might identify novel therapeutic targets and diagnostic biomarkers.

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Section: Autophagy Induction and Intracellular Replication In Viral Ccontrasting

confidence: 81%

Interactions between neurotropic pathogens, neuroinflammatory pathways, and autophagic neural cell death

Sahu¹,

Ter²

2018

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“…Inappropriate activation of the antiviral response can lead to cytotoxicity and cell death (30). We and others have demonstrated an IFN-␤-mediated antiviral response during JEV infection (31)(32)(33)(34). Recent studies have shown that miRNAs, such as miR-146, miR-155, and miR-203, are involved in regulating type I IFN signaling (30,35).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA 155 Regulates Japanese Encephalitis Virus-Induced Inflammatory Response by Targeting Src Homology 2-Containing Inositol Phosphatase 1

Thounaojam

Kundu

Kaushik

et al. 2014

J Virol

114

130

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MicroRNAs (miRNAs) are single-stranded small RNA molecules that regulate various cellular processes. miRNA 155 (miR-155) regulates various aspects of innate and adaptive immune responses and plays a key role in various viral infections and the resulting neuroinflammation. The present study evaluated the involvement of miR-155 in modulating Japanese encephalitis virus (JEV)-induced neuroinflammation. We observed that miR-155 expression was upregulated during JEV infection of mouse primary microglia, the BV-2 microglia cell line, and in both mouse and human brains. In vitro and in vivo knockdown of miR-155 minimized JEV-induced inflammatory responses. In the present study, we confirmed targeting of the Src homology 2-containing inositol phosphatase 1 (SHIP1) 3= untranslated region (UTR) by miR-155 in the context of JEV infection. Inhibition of SHIP1 by miR-155 resulted in higher beta interferon (IFN-␤) and proinflammatory cytokine production through activation of TANKbinding kinase 1 (TBK-1). Based on these observations, we conclude that miR-155 modulates the neuroinflammatory response during JEV infection via negative regulation of SHIP1 expression. Thus, modulation of miR-155 could be a novel strategy to regulate JEV-induced neuroinflammation. IMPORTANCE Japanese encephalitis virus (JEV), a member of the family Flaviviridae that causes Japanese encephalitis (JE), is the most common mosquito-borne encephalitis virus in the Japanese encephalitis virus (JEV), a member of the family Flaviviridae, is a single-stranded, positive-sense RNA virus that causes Japanese encephalitis (JE) (1, 2). JE is endemic in most Southeast Asian countries (3, 4). The availability of an effective vaccine and an active immunization program have resulted in a reduced number of JE cases in a few countries (5). The early clinical features of JE include fever, headache, and vomiting. Two weeks after JEV infection, patients develop neurological symptoms, like seizure, tremor, photophobia, and movement disorder (6). These clinical features are not exclusive to JEV infection, and hence, laboratory diagnosis is needed to differentiate it from other neurological disorders. Detection of anti-JEV IgM antibodies in the cerebrospinal fluid (CSF) and serum is frequently used to diagnose JE (7). The fatality rate of JEV infection is ϳ25%. A majority of survivors (ϳ50%) have neuropsychiatric sequelae; only ϳ25% recover completely (8). Hence, JEV poses major health concerns and economic burdens in the Asia-Pacific region. During the last decade, we and others have made significant progress in the understanding molecular mechanisms involved in JEV infection.MicroRNAs (miRNAs) are small, noncoding RNAs ϳ19 to 22 nucleotides in length that regulate various cellular processes by binding to the 3= untranslated region (UTR) of target proteins, resulting in either degradation of RNA or translational suppression (9, 10). Our knowledge of the role of miRNAs in various diseases is expanding rapidly. Various reports support the role of miRNAs in neuroviral...

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“…Recently, Japanese encephalitis virus (JEV) has been shown to subvert autophagy as a viral immune evasion strategy. The mechanism may be similar to that used by HCV, since type I IFN activation is increased when JEV infects cells deficient in autophagy (77). Infection with JEV increases autolysosome formation in vivo, and this formation is essential for maximum virus production (77).…”

Section: Possible Connections Among Viruses That Benefit From Autophamentioning

confidence: 99%

“…The mechanism may be similar to that used by HCV, since type I IFN activation is increased when JEV infects cells deficient in autophagy (77). Infection with JEV increases autolysosome formation in vivo, and this formation is essential for maximum virus production (77). Is it not yet known if autophagic degradation is responsible for restriction of the immune response during JEV infection.…”

Section: Possible Connections Among Viruses That Benefit From Autophamentioning

confidence: 99%

How Positive-Strand RNA Viruses Benefit from Autophagosome Maturation

Richards

Jackson

2013

J Virol

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The autophagic degradation pathway is a powerful tool in the host cell arsenal against cytosolic pathogens. Contents trapped inside cytosolic vesicles, termed autophagosomes, are delivered to the lysosome for degradation. In spite of the degradative nature of the pathway, some pathogens are able to subvert autophagy for their benefit. In many cases, these pathogens have developed strategies to induce the autophagic signaling pathway while inhibiting the associated degradation activity. One surprising finding from recent literature is that some viruses do not impede degradation but instead promote the generation of degradative autolysosomes, which are the endpoint compartments of autophagy. Dengue virus, poliovirus, and hepatitis C virus, all positivestrand RNA viruses, utilize the maturation of autophagosomes into acidic and ultimately degradative compartments to promote their replication. While the benefits that each virus reaps from autophagosome maturation are unique, the parallels between the viruses indicate a complex relationship between cytosolic viruses and host cell degradation vesicles.

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Japanese Encephalitis Virus Activates Autophagy as a Viral Immune Evasion Strategy

Cited by 77 publications

References 45 publications

Interactions between neurotropic pathogens, neuroinflammatory pathways, and autophagic neural cell death

Interactions between neurotropic pathogens, neuroinflammatory pathways, and autophagic neural cell death

MicroRNA 155 Regulates Japanese Encephalitis Virus-Induced Inflammatory Response by Targeting Src Homology 2-Containing Inositol Phosphatase 1

How Positive-Strand RNA Viruses Benefit from Autophagosome Maturation

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