scholarly journals Impaired cross-presentation of CD8α+CD11c+dendritic cells by Japanese encephalitis virus in a TLR2/MyD88 signal pathway-dependent manner

2012 ◽  
Vol 42 (10) ◽  
pp. 2655-2666 ◽  
Author(s):  
Abi G. Aleyas ◽  
Young Woo Han ◽  
Ajit Mahadev Patil ◽  
Seong Bum Kim ◽  
Koanhoi Kim ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Signal Pathway ◽  
Encephalitis Virus ◽  
Dependent Manner ◽  
Cross Presentation

scholarly journals Human MxB Inhibits the Replication of Hepatitis C Virus

2018 ◽  
Vol 93 (1) ◽  
Author(s):  
Dong-Rong Yi ◽  
Ni An ◽  
Zhen-Long Liu ◽  
Feng-Wen Xu ◽  
Kavita Raniga ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Dengue Virus ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Rna Replication ◽  
Encephalitis Virus ◽  
Common Mechanism ◽  
Type I ◽  
Dependent Manner

ABSTRACTType I interferon (IFN) inhibits viruses by inducing the expression of antiviral proteins. The IFN-induced myxovirus resistance B (MxB) protein has been reported to inhibit a limited number of viruses, including HIV-1 and herpesviruses, but its antiviral coverage remains to be explored further. Here we show that MxB interferes with RNA replication of hepatitis C virus (HCV) and significantly inhibits viral replication in a cyclophilin A (CypA)-dependent manner. Our data further show that MxB interacts with the HCV protein NS5A, thereby impairing NS5A interaction with CypA and NS5A localization to the endoplasmic reticulum, two events essential for HCV RNA replication. Interestingly, we found that MxB significantly inhibits two additional CypA-dependent viruses of theFlaviviridaefamily, namely, Japanese encephalitis virus and dengue virus, suggesting a potential link between virus dependence on CypA and virus susceptibility to MxB inhibition. Collectively, these data have identified MxB as a key factor behind IFN-mediated suppression of HCV infection, and they suggest that other CypA-dependent viruses may also be subjected to MxB restriction.IMPORTANCEViruses of theFlaviviridaefamily cause major illness and death around the world and thus pose a great threat to human health. Here we show that IFN-inducible MxB restricts several members of theFlaviviridae, including HCV, Japanese encephalitis virus, and dengue virus. This finding not only suggests an active role of MxB in combating these major pathogenic human viruses but also significantly expands the antiviral spectrum of MxB. Our study further strengthens the link between virus dependence on CypA and susceptibility to MxB restriction and also suggests that MxB may employ a common mechanism to inhibit different viruses. Elucidating the antiviral functions of MxB advances our understanding of IFN-mediated host antiviral defense and may open new avenues to the development of novel antiviral therapeutics.

scholarly journals Japanese Encephalitis Virus Infected Microglial Cells Secrete Exosomes Containing let-7a/b that Facilitate Neuronal Damage via Caspase Activation

2018 ◽  
Author(s):  
Sriparna Mukherjee ◽  
Irshad Akbar ◽  
Bharti Kumari ◽  
Sudhanshu Vrati ◽  
Anirban Basu ◽  
...  
Keyword(s):  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Neuronal Damage ◽  
Cell Communication ◽  
Notch Signaling Pathway ◽  
Encephalitis Virus ◽  
Microglial Cells ◽  
Dependent Manner ◽  
Caspase Activation ◽  
Hek 293

AbstractExtracellular microRNAs (miRNAs) are essential for the cell to cell communication in the healthy and diseased brain. MicroRNAs released from the activated microglia upon neurotropic virus infection may exacerbate CNS damage. Here, we identified let-7a and let-7b (let-7a/b) as the overexpressed miRNAs in Japanese Encephalitis virus (JEV) infected microglia and assessed their role in JEV pathogenesis. We measured the let-7a/b expressions in JEV infected post-mortem human brains, mice brains and in mouse microglial N9 cells by the qRT-PCR and in situ hybridization assay. The interaction between let-7a/b and NOTCH signaling pathway further examined in Toll-like receptor 7 knockdown (TLR7 KD) mice to assess the functions. Exosomes released from JEV infected or let-7a/b mimic transfected N9, and HEK-293 cells were isolated and evaluated their function. We observed an upregulation of let-7a/b in the infected brains as well as in microglia. Knockdown of TLR7 or Inhibition of let-7a/b suppressed the JEV induced NOTCH activation possibly via NF-κB dependent manner and subsequently, attenuated JEV induced TNFα production in microglial cells. Further, exosomes secreted from JEV-infected microglial cells specifically contained let-7a/b. Exosomes overexpressed with let-7a/b were injected into BALB/c mice as well as co-incubated with mouse neuronal (Neuro2a) cells, or primary cortical neuron resulted in caspase activation leading to neuronal damage in the brain. Thus, our results provide evidence for the multifaceted role of let-7a/b miRNAs and unravel the exosomes mediated mechanism for JEV induced pathogenesis.

scholarly journals Antiviral effect of dehydroepiandrosterone on Japanese encephalitis virus infection

2005 ◽  
Vol 86 (9) ◽  
pp. 2513-2523 ◽  
Author(s):  
Chia-Che Chang ◽  
Yen-Chuan Ou ◽  
Shue-Ling Raung ◽  
Chun-Jung Chen
Keyword(s):  
Cell Death ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Apoptotic Cell ◽  
Antiviral Effect ◽  
Encephalitis Virus ◽  
Apoptotic Cell Death ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Japanese Encephalitis Virus Infection

Japanese encephalitis virus (JEV), which causes neurological disorders, completes its life cycle and triggers apoptotic cell death in infected cells. Dehydroepiandrosterone (DHEA), an adrenal-derived steroid, has been implicated in protection against neurotoxicity and protection of animals from viral-induced encephalitis, resulting in an increased survival rate of the animals. Currently, the mechanisms underlying the beneficial effects of DHEA against the virus are largely unknown. In this study, DHEA suppression of JEV replication and virus-induced apoptosis in murine neuroblastoma (N18) cells was investigated. It was found that DHEA suppressed JEV-induced cytopathic effects, JEV-induced apoptotic cell death and JEV propagation in a concentration-dependent manner. Antiviral activity was more efficient in cultures treated with DHEA immediately after viral adsorption compared with that in cultures receiving delayed administration after adsorption or transient exposure before adsorption. JEV-induced cytotoxicity was accompanied by the inactivation of extracellular signal-regulated protein kinase (ERK). Inactivation of ERK by JEV infection was reversed by DHEA. When cells were treated with the ERK inhibitor U0126, DHEA lost its antiviral effect. Activation of ERK by anisomycin mimicked the action of DHEA in suppressing JEV-induced cytotoxicity. DHEA-related compounds, such as its sulfate ester (DHEAS) and pregnenolone, were unable to suppress JEV-induced cytotoxicity and ERK inactivation. The hormone-receptor antagonists ICI 182780 and flutamide failed to abrogate the antiviral effect of DHEA. These findings suggest that the antiviral effect of DHEA is not linked directly to the genomic steroid-receptor pathways and suggest that the signalling pathways of ERK play a role in the antiviral action of DHEA.

scholarly journals Blocking of the Alpha Interferon-Induced Jak-Stat Signaling Pathway by Japanese Encephalitis Virus Infection

2004 ◽  
Vol 78 (17) ◽  
pp. 9285-9294 ◽  
Author(s):  
Ren-Jye Lin ◽  
Ching-Len Liao ◽  
Elong Lin ◽  
Yi-Ling Lin
Keyword(s):  
Japanese Encephalitis Virus ◽  
Signaling Pathway ◽  
Tyrosine Phosphorylation ◽  
Japanese Encephalitis ◽  
Encephalitis Virus ◽  
Janus Kinase ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Stat Signaling ◽  
Infected Cells

ABSTRACT The induction of alpha/beta interferon (IFN-α/β) is a powerful host defense mechanism against viral infection, and many viruses have evolved strategies to overcome the antiviral effects of IFN. In this study, we found that IFN-α had only some degree of antiviral activity against Japanese encephalitis virus (JEV) infection, in contrast to another flavivirus, dengue virus serotype 2, which was highly sensitive to IFN-α in the cultured cell system. JEV infection appeared to render cells resistant to IFN-α since the IFN-α-induced luciferase reporter activity driven by the IFN-stimulated response element (ISRE) was gradually reduced as the JEV infection progressed. Since the biological activities of IFNs are triggered by the Janus kinase (Jak) signal transducer and activation of transcription (Stat) signaling cascade, we then studied the activation of Jak-Stat pathway in the virus-infected cells. The IFN-α-stimulated tyrosine phosphorylation of Stat1, Stat2, and Stat3 was suppressed by JEV in a virus replication and de novo protein synthesis-dependent manner. Furthermore, JEV infection blocked the tyrosine phosphorylation of IFN receptor-associated Jak kinase, Tyk2, without affecting the expression of IFN-α/β receptor on the cell surface. Consequently, expression of several IFN-stimulated genes in response to IFN-α stimulation was also reduced in the JEV-infected cells. Overall, our findings suggest that JEV counteracts the effect of IFN-α/β by blocking Tyk2 activation, thereby resulting in inhibition of Jak-Stat signaling pathway.

scholarly journals Japanese encephalitis virus infection activates caspase-8 and -9 in a FADD-independent and mitochondrion-dependent manner

2008 ◽  
Vol 89 (8) ◽  
pp. 1930-1941 ◽  
Author(s):  
Chang-Huei Tsao ◽  
Hong-Lin Su ◽  
Yi-Ling Lin ◽  
Han-Pang Yu ◽  
Shu-Ming Kuo ◽  
...  
Keyword(s):  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Caspase 3 ◽  
Encephalitis Virus ◽  
Dominant Negative Mutant ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Caspase 9 ◽  
Effector Caspase ◽  
Induced Apoptosis

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, replicates primarily at the endoplasmic reticulum and thereby triggers apoptosis of infected cells. This study investigated the hierarchical activation of the caspase network induced by JEV infection. It was found that JEV activated the initiators caspase-8 and -9, as well as effector caspase-3, in infected baby hamster kidney and mouse neuroblastoma (N18) cells. In neuronal N18 cells, JEV infection triggered cytochrome c release from mitochondria, which in turn activated caspase-9 and -3. Treatment of JEV-infected N18 cells with cyclosporin A or ruthenium red, which attenuate mitochondrial injuries, blocked activation of caspase-9 or -3, typifying that, in neuronal cells, this apoptosis involves the mitochondrial pathway. Alternatively, in caspase-3-deficient MCF-7 cells, JEV persisted and readily triggered a typical apoptotic response, including cytochrome c release and full activation of caspase-9 and -8 along with caspase-6, indicating that JEV did not require caspase-3 to manifest caspase-8 activation and apoptosis. Interestingly, a Fas-associated death-domain-containing protein (FADD) dominant-negative mutant, which interfered with transmission of the extracellular death signals into cells through the Fas/tumour necrosis factor (TNF) receptor, failed to block JEV-induced apoptosis and caspase-8 activation, implying that receptor oligomerization of the Fas/TNF pathway might not participate in JEV-induced apoptosis. Taken together, these results illustrate that JEV infection triggers caspase cascades involving the initiators caspase-8 and -9, probably through FADD-independent but mitochondrion-dependent pathways.

scholarly journals Hsp40 Protein DNAJB6 Interacts with Viral NS3 and Inhibits the Replication of the Japanese Encephalitis Virus

2019 ◽  
Vol 20 (22) ◽  
pp. 5719
Author(s):  
Yu-Qin Cao ◽  
Lei Yuan ◽  
Qin Zhao ◽  
Jian-Lin Yuan ◽  
Chang Miao ◽  
...  
Keyword(s):  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Viral Entry ◽  
Time Course ◽  
Encephalitis Virus ◽  
Regulatory Function ◽  
Dependent Manner ◽  
Structural Protein ◽  
Viral Binding ◽  
East And Southeast Asia

The Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus prevalent in east and southeast Asia, the Western Pacific, and northern Australia. Since viruses are obligatory intracellular pathogens, the dynamic processes of viral entry, replication, and assembly are dependent on numerous host-pathogen interactions. Efforts to identify JEV-interacting host factors are ongoing because their identification and characterization remain incomplete. Three enzymatic activities of flavivirus non-structural protein 3 (NS3), including serine protease, RNA helicase, and triphosphatase, play major roles in the flaviviruses lifecycle. To identify cellular factors that interact with NS3, we screened a human brain cDNA library using a yeast two-hybrid assay, and identified eight proteins that putatively interact with NS3: COPS5, FBLN5, PPP2CB, CRBN, DNAJB6, UBE2N, ZNF350, and GPR137B. We demonstrated that the DnaJ heat shock protein family (Hsp40) member B6 (DNAJB6) colocalizes and interacts with NS3, and has a negative regulatory function in JEV replication. We also show that loss of DNAJB6 function results in significantly increased viral replication, but does not affect viral binding or internalization. Moreover, the time-course of DNAJB6 disruption during JEV infection varies in a viral load-dependent manner, suggesting that JEV targets this host chaperone protein for viral benefit. Deciphering the modes of NS3-interacting host proteins functions in virion production will shed light on JEV pathogenic mechanisms and may also reveal new avenues for antiviral therapeutics.

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