Targeting transient receptor potential channels to suppress proviral mitochondrial fission and mitophagy in order to mitigate CVB pancreatitis
靶向瞬时受体电位通道抑制原病毒线粒体裂变和线粒体自噬以减轻 CVB 胰腺炎
基本信息
- 批准号:10578775
- 负责人:
- 金额:$ 31.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-12-07 至 2025-12-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAffectAntibody titer measurementAntiviral TherapyAreaAttenuatedCapsaicinCardiac MyocytesCellsCessation of lifeChildCoxsackie B VirusesCoxsackie VirusesCytoplasmDataDiagnosisDiseaseDisease ProgressionEnterovirusEnzymesExocrine pancreasHela CellsHumanImpairmentIn VitroInfectionInflammationInflammatoryIon ChannelMalignant neoplasm of cervix uteriMalignant neoplasm of pancreasMediatingMeningoencephalitisMentholMitochondriaMitochondrial RNAMusMyocarditisNonlyticOralOrganPancreasPancreatitisPathway interactionsPatientsPeptide HydrolasesPlayPredispositionProcessProductionReportingRibosomesRisk FactorsRoleSeveritiesSignal TransductionSymptomsTRP channelTRPV1 geneTestingTranslatingTranslationsTropismViralViral Load resultViral PathogenesisViral ProteinsVirusVirus DiseasesVirus Replicationacute pancreatitisantagonistantiviral immunitycancer cellchronic pancreatitiseffective interventionextracellular vesicleshigh riskhuman pathogeninsightmortalitymouse modelneutralizing antibodynovelnovel therapeuticsprematurepreventpromoterreceptorsystemic inflammatory responseviral RNA
项目摘要
PROJECT SUMMARY
Coxsackievirus B (CVB) is a common human pathogen that can cause an array of inflammatory diseases such
as meningo-encephalitis, myocarditis and pancreatitis. CVB has strong tropism to the pancreas and as such is
a leading cause of viral pancreatitis. Acute pancreatitis can sometimes be severe, which leads to systemic
inflammation, damage to other organs and death in 10-30% of patients. Children are at higher risk for lethal CVB
pancreatitis. CVB can also cause chronic pancreatitis, which is a persistent inflammation of the pancreas that is
a risk factor for pancreatic cancer. Treatments for severe viral pancreatitis generally aim to mitigate symptoms,
however there is a lack of effective interventions that limit disease progression. In a recent study we had reported
that CVB type 3 (CVB3) infection causes mitochondrial fission with subsequent activation of mitophagy in
infected cells. We surmise that CVB3 triggers this in order to become engulfed in mitophagosomes which
become expelled from the host cell as virus-laden extracellular vesicles. Specifically blocking mitochondrial
fission or mitophagy pathways disrupts this process and attenuates infection. In recent reports, the transient
receptor potential (TRP) ion channels have been shown to influence mitochondrial dynamics. The capsaicin and
heat receptor TRPV1 can trigger mitochondrial depolarization which leads to mitochondrial fragmentation. We
have found that inhibiting TRPV1 not only prevents CVB3-induced mitochondrial fission, but also significantly
reduces infection in vitro. Similarly, activating the TRPV1 antagonist TRPM8 using menthol also greatly blunts
infection. We tested the effects of oral menthol treatments in a mouse model of pancreatic CVB3 infection and
saw that menthol blunts pancreatic damage and viral load. There is very limited data on how TRP channels
influence viral infection. Understanding how these pathways influence CVB3 infection will allow us to establish
novel antiviral treatments (such as menthol) to be used to suppress CVB3 pancreatitis as well as other CVB3-
induced diseases.
项目总结
项目成果
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{{ truncateString('Jon Sin', 18)}}的其他基金
Targeting transient receptor potential channels to suppress proviral mitochondrial fission and mitophagy in order to mitigate CVB pancreatitis
靶向瞬时受体电位通道抑制原病毒线粒体裂变和线粒体自噬以减轻 CVB 胰腺炎
- 批准号:
10535247 - 财政年份:2021
- 资助金额:
$ 31.38万 - 项目类别:
Targeting transient receptor potential channels to suppress proviral mitochondrial fission and mitophagy in order to mitigate CVB pancreatitis
靶向瞬时受体电位通道抑制原病毒线粒体裂变和线粒体自噬以减轻 CVB 胰腺炎
- 批准号:
10208569 - 财政年份:2021
- 资助金额:
$ 31.38万 - 项目类别:
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