# Targeting transient receptor potential channels to suppress proviral mitochondrial fission and mitophagy in order to mitigate CVB pancreatitis

> **NIH NIH R01** · UNIVERSITY OF ALABAMA IN TUSCALOOSA · 2024 · $295,931

## Abstract

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.

## Key facts

- **NIH application ID:** 10765670
- **Project number:** 5R01DK125692-04
- **Recipient organization:** UNIVERSITY OF ALABAMA IN TUSCALOOSA
- **Principal Investigator:** Jon Sin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $295,931
- **Award type:** 5
- **Project period:** 2021-12-07 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765670

## Citation

> US National Institutes of Health, RePORTER application 10765670, Targeting transient receptor potential channels to suppress proviral mitochondrial fission and mitophagy in order to mitigate CVB pancreatitis (5R01DK125692-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10765670. Licensed CC0.

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