PLVAP and GKN3 Are Two Critical Host Cell Receptors Which Facilitate Japanese Encephalitis Virus Entry Into Neurons

Mukherjee, Sriparna; Sengupta, Nabonita; Chaudhuri, Ankur; Akbar, Irshad; Singh, Noopur; Chakraborty, Sibani; Suryawanshi, Amol Ratnakar; Bhattacharyya, Arindam; Basu, Anirban

doi:10.1038/s41598-018-30054-z

Cited by 40 publications

(26 citation statements)

References 39 publications

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“…GKN3 is a gastrokine that is expressed specifically in the stomach, but its function is obscure. GKN3 expression has been found to be upregulated in gastric antral tumorigenesis and Japanese encephalitis virus‐infected brain tissues. It was reported that GKN2 forms heterodimers with TFF1 in stomach mucosal cells and regulates the extracellular function of TFFs.…”

Section: Discussionmentioning

confidence: 99%

Early administration of dapagliflozin preserves pancreatic β‐cell mass through a legacy effect in a mouse model of type 2 diabetes

Kanno

Asahara

Kawamura

et al. 2018

J of Diabetes Invest

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Aims/Introduction The preservation of pancreatic β‐cell mass is an essential factor in the onset and development of type 2 diabetes mellitus. Recently, sodium–glucose cotransporter 2 inhibitors have been launched as antihyperglycemic agents, and their organ‐protective effects are attracting attention. They are also reported to have favorable effects on the preservation of pancreatic β‐cell mass, but the appropriate timing for the administration of sodium–glucose cotransporter 2 inhibitors is obscure. Materials and Methods In the present study, we administered a sodium–glucose cotransporter 2 inhibitor, dapagliflozin, to an animal model of type 2 diabetes mellitus, db / db mice, and investigated the adequate timing and duration for its administration. We also carried out microarray analysis using pancreatic islets from db / db mice. Results We found that dapagliflozin preserved pancreatic β‐cell mass depending on the duration of administration and markedly improved blood glucose levels. If the duration was the same, the earlier administration of dapagliflozin was more effective in preserving pancreatic β‐cell mass, increasing serum insulin levels and improving blood glucose levels. From microarray analysis, we discovered that the expression of Agr2 , Tff2 and Gkn3 was significantly upregulated after the early administration of dapagliflozin. This upregulated gene expression might provide a legacy effect for the preservation of pancreatic β‐cell mass. Conclusions We expect that the early administration of dapagliflozin would provide a long‐lasting effect in preserving pancreatic β‐cell mass.

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Section: Discussionmentioning

confidence: 99%

Early administration of dapagliflozin preserves pancreatic β‐cell mass through a legacy effect in a mouse model of type 2 diabetes

Kanno

Asahara

Kawamura

et al. 2018

J of Diabetes Invest

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“…Mouse cortical neurons were cultured as per previously-mentioned protocol (34). Briefly, 2-day old BALB/c mouse pups’ brain cortex was isolated in calcium and magnesium-free tyrode solution, under a dissecting microscope and sterile conditions.…”

Section: Methodsmentioning

confidence: 99%

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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“…Usually, encephalitis is the most severe clinical appearance of JEV infection with a variety of first symptoms, including seizures, as well as acute sensory and neuromuscular functional deficiencies [119]. JEV infection of microglia [113,120], astrocytes [121] and neurons [122,123,124,125] with corresponding cellular response and possible apoptosis, as well as subsequent inflammatory response results in neuronal cell death. In addition, oedema and vascular damage may enhance damage to the tissue and cells.…”

Section: Jev Crossing the Blood–brain Barrier And Brain Infectionmentioning

confidence: 99%

Review of Emerging Japanese Encephalitis Virus: New Aspects and Concepts about Entry into the Brain and Inter-Cellular Spreading

Filgueira

Lannes

2019

Pathogens

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Japanese encephalitis virus (JEV) is an emerging flavivirus of the Asia-Pacific region. More than two billion people live in endemic or epidemic areas and are at risk of infection. Recently, the first autochthonous human case was recorded in Africa, and infected birds have been found in Europe. JEV may spread even further to other continents. The first section of this review covers established and new information about the epidemiology of JEV. The subsequent sections focus on the impact of JEV on humans, including the natural course and immunity. Furthermore, new concepts are discussed about JEV’s entry into the brain. Finally, interactions of JEV and host cells are covered, as well as how JEV may spread in the body through latently infected immune cells and cell-to-cell transmission of virions or via other infectious material, including JEV genomic RNA.

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PLVAP and GKN3 Are Two Critical Host Cell Receptors Which Facilitate Japanese Encephalitis Virus Entry Into Neurons

Cited by 40 publications

References 39 publications

Early administration of dapagliflozin preserves pancreatic β‐cell mass through a legacy effect in a mouse model of type 2 diabetes

Early administration of dapagliflozin preserves pancreatic β‐cell mass through a legacy effect in a mouse model of type 2 diabetes

Novel strategy for treating neurotropic viral infections using hypolipidemic drug Atorvastatin

Review of Emerging Japanese Encephalitis Virus: New Aspects and Concepts about Entry into the Brain and Inter-Cellular Spreading

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