Japanese Encephalitis Virus‐induced <i>let‐7a/b</i> interacted with the <scp>NOTCH</scp>‐<scp>TLR</scp>7 pathway in microglia and facilitated neuronal death via caspase activation

Mukherjee, Sriparna; Akbar, Irshad; Kumari, Bharti; Vrati, Sudhanshu; Basu, Anirban; Banerjee, Arup

doi:10.1111/jnc.14645

Cited by 61 publications

(42 citation statements)

References 42 publications

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“…5´-ATGGATATAGAAAATGAGCAGAC-3´ and 5´-CCAGATCTGGACCGCCTATC-3´ sequences were used as forward and reverse primers for the quantification of PDCD4 mRNA. Thermocycling conditions used for determination of PDCD4 abundance has been mentioned earlier (35). Isolation of miRNA and cDNA preparation were performed as described earlier (35).…”

Section: Methodsmentioning

confidence: 99%

“…Thermocycling conditions used for determination of PDCD4 abundance has been mentioned earlier (35). Isolation of miRNA and cDNA preparation were performed as described earlier (35). Sequences 5ʹ-UAGCUUAUCAGACUGAUGUUGA-3ʹ and 5ʹ-UAGCUUAUCAGACUGAUGUUGA-3ʹ were used as forward primers in qRT-PCR analysis of human and mouse miR-21 respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Human autopsy tissue samples were collected from the Human Brain Bank, NIMHANS, Bangalore, as per institutional ethics and confidentiality of the subjects. miRNA isolation from human brain sections was performed using methods as described previously (35). Expression data for snRNA SNORD68 was used as a normalization control.…”

Section: Methodsmentioning

confidence: 99%

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Novel strategy for treating neurotropic viral infections using hypolipidemic drug Atorvastatin

Mallick¹,

Chakraborty²,

Hazra³

et al. 2019

Preprint

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18Chandipura virus (CHPV) and Japanese Encephalitis Virus (JEV) are known to infect neurons 19 followed by their successful propagation. Increased incidences of central nervous system 20 invasion by the abovementioned viruses have been reported in case of children and elderly thus 21 culminating into severe neurological damage. Literature suggests induction of endoplasmic 22 reticulum (ER)-stress related proteins upon CHPV and JEV infection which help promote viral 23 reproduction. Since earlier studies underscore the pleotropic role of atorvastatin (AT) in 24 neuroprotection against flaviviruses like Hepatitis C and dengue, it was hypothesized that AT 25 might also act as a neuroprotective agent against RNA viruses like CHPV and JEV. AT-26 mediated antiviral activity was evaluated by assessing survivability of virus-infected mouse pups 27 treated with the drug. Balb C mice were used for in vivo experiments. Neuro2A cell line was 28 used as the model for in vitro experiments. Cells subjected to AT treatment were infected by 29 CHPV and JEV followed by evaluation of ER stress-related and apoptosis-related proteins by 30 immunoblotting technique and immunofluorescence microscopy. Interaction of host protein with 31 viral genome was assessed by RNA-Co-IP. AT treatment exhibited significant anti-viral activity 32 against CHPV and JEV infections via hnRNPC-dependent manner. Viral genome-hnRNPC 33 interaction was found to be abrogated upon AT action. AT was also observed to reduce secretion 34 of proinflammatory cytokines by the neurons in response to viral infection. Moreover, AT 35 treatment was also demonstrated to reduce neuronal death by abrogating virus-induced miR-21 36 upregulation in hnRNPC-dependent fashion. This study thus suggests probable candidature of 37 AT as antiviral against CHPV and JEV infections.38 Introduction: 39 Incidences of Acute Encephalitis Syndrome (AES) resulting from infection by neurotropic RNA 40 viruses like Japanese Encephalitis Virus (JEV) and Chandipura Virus (CHPV) have been 41 reported in India on an annual basis (1). Both JEV and CHPV are arboviruses differing in terms 42 of genetic material. JEV possesses a single positive-stranded RNA as genetic material, while 43 CHPV is a negative-stranded RNA virus (2, 3). JEV is being reported to mainly target central 44 nervous system (CNS) of children. Since CNS of infants undergo a lot of physiological changes 45 as development progresses, any insult to neuronal physiology may lead to severe perturbation of 46 neurocognitive abilities thus leaving the survivors of JEV-induced encephalitis with motor 47 deficits, cognitive and language impairments and learning difficulties (4, 5). Whereas, although 48 infection due to CHPV leads to acute encephalopathy, no report till date documents incidences of 49 neurological sequel experienced by survivors of CHPV-induced encephalitis (5). Evidences 50 suggest neuronal death following JEV or CHPV infections by two distinct mechanisms. In 51 addition to direct viral propagation-mediated neuronal res...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Novel strategy for treating neurotropic viral infections using hypolipidemic drug Atorvastatin

Mallick¹,

Chakraborty²,

Hazra³

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…For experiments, pups of either sex were randomly divided into two groups: Sham-treated and JEV-infected. Mice belonging to the JEV-infected group were injected with 3 x 10 5 PFU of GP-78 strain intraperitoneally, while an equal amount of sterile PBS was injected into the sham-treated group (Mukherjee, Akbar et al, 2019). Infected pups, along with sham-treated animals, were euthanized on day seven post-infection after the encephalitis symptoms appeared (Hazra, Chakraborty et al, 2019, Sengupta, Ghosh et al, 2014.…”

Section: Jev Infection In Micementioning

confidence: 99%

Retinoic Acid Inducible Gene-I like Receptors Activate Snail and Slug to Limit RNA Viral Infections

Vedagiri

Gupta

Mishra

et al. 2020

Preprint

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Several viruses have been reported to induce EMT in culture models, with their functional relevance remaining under-studied. Here, by linking the activation of EMT-TFs Snail and Slug by RLRs and the widespread observation of EMT by RNA viruses, we propose that EMT is a general cellular response in epithelial cells to RNA viral infections. Using viral genomic RNA and dsRNA analog transfection models, we identify that viral RNAs are strong inducers of EMT-TFs Snail and Slug, which required the phosphorylation of IRF3 by RLRs. Importantly, the ISRE elements that we identified in the SNAI1 promoter were critical for this transcriptional activation. Over-expressing Snail or Slug significantly elevated the RLR levels, TBK1 and STAT1 phosphorylations and several ISGs, providing the cells with higher refractoriness to RNA viruses. This antiviral property of these EMT-TFs is indicative of their unidentified roles in innate immune response, which position them as potential antiviral regulators. Together, our studies demonstrate a previously unidentified mechanism of activation of Snail and Slug and establish a new paradigm for their functions in innate immunity.

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“…JEV infects a variety of cell types from diverse species (including mammals, birds, amphibians, and insects), suggesting that JEV can likely access multiple cell types using multiple host receptors 14 . In recent years, tremendous progress has been made in understanding the viral components required for the various steps of JEV entry and replication, but little is known about the host cell components involved in this process [15][16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

CRISPR screening of porcine sgRNA library identified host factors essential for Japanese encephalitis virus replication

Zhao

Liu

Xiao

et al. 2019

Preprint

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Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus that causes encephalitis and reproductive disorders in mammalian species. However, key host genes involved in the JEV life cycle and cell death are poorly understood. Here, we designed 85,674 single guide RNAs (sgRNAs) targeting 17,743 protein-coding genes, 11,053 long ncRNAs (lncRNAs), and 551 microRNAs (miRNAs) in the porcine genome, and subsequently developed a porcine sgRNA library and genome-scale CRISPR/Cas9 knockout (PigGeCKO) system. These sgRNAs were delivered into porcine kidney-15 (PK-15) cells that constitutively express Cas9, positive selection screening of the resulting PigGeCKO cell collection for resistance to JEV-induced cell death led to the identification of several previously unreported genes required for JEV infection. We conducted follow-up studies to verify the dependency of JEV on these genes, and identified functional contributions for six of the many candidate JEV-related host genes, including an endoplasmic reticulum membrane protein complex subunit 3 (EMC3) and calreticulin (CALR). Additionally, we identified that four genes associated with heparan sulfate proteoglycans (HSPGs) metabolism, specifically those responsible for HSPG sulfurylation, facilitated JEV entry into PK-15 cells. Thus, beyond our development of the largest CRISPR-based functional genomic screening platform for pig research to date, this work deepens our basic understanding of flavivirus infection and identifies multiple potentially vulnerable targets for the development of medical and breeding technologies to prevent and treat diseases caused by Japanese encephalitis virus.

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Japanese Encephalitis Virus‐induced let‐7a/b interacted with the NOTCH‐TLR7 pathway in microglia and facilitated neuronal death via caspase activation

Cited by 61 publications

References 42 publications

Novel strategy for treating neurotropic viral infections using hypolipidemic drug Atorvastatin

Novel strategy for treating neurotropic viral infections using hypolipidemic drug Atorvastatin

Retinoic Acid Inducible Gene-I like Receptors Activate Snail and Slug to Limit RNA Viral Infections

CRISPR screening of porcine sgRNA library identified host factors essential for Japanese encephalitis virus replication

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