Cell reportsSep 2, 2025

Coxsackievirus B triggers unique responses in different cell types of human pancreatic islets

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

Coxsackievirus B (CVB3) induces distinct cell-type-specific responses in human islet cells.

CVB3 impacts transcriptional and mitochondrial activity in human cadaveric islets.
No preferential infection rates were found for β and ductal cells; both endocrine and exocrine cells were comparably affected.
Ductal cells exhibited the strongest responses related to interferon and HLA, contrary to previous beliefs about β cells.
The long non-coding RNA MIR7-3HG influences viral RNA levels, viral load, cell death, and cellular recycling processes when silenced.
These results challenge existing views on viral targeting in islet cells and highlight specific cellular reactions to CVB3 that may be relevant to type 1 diabetes.

Simplified

Coxsackievirus B (CVB) is implicated as an environmental trigger for type 1 diabetes (T1D). While CVB impairs islet function and viability, its impact on individual primary human islet cell types remains unclear. Here, we use single-cell RNA sequencing and functional studies to show that CVB3 induces distinct cell-type-specific transcriptional and mitochondrial responses in human cadaveric islets. Contrary to prior claims, our analysis reveals no evidence of preferential viral tropism for β and ductal cells, instead demonstrating comparable infection rates across both endocrine and exocrine compartments. β, α, and ductal cells show the most robust transcriptional responses to infection, with ductal cells, not β cells, exhibiting the strongest interferon- and HLA-associated responses. Notably, the long non-coding MIR7-3HG modulates viral RNA expression, titer, apoptosis, and autophagy upon knockdown in stem-cell-derived islets. These findings challenge long-standing assumptions about islet-specific viral targeting and demonstrate cell-specific responses to CVB3 infection relevant to T1D.

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Competing interests

Declaration of interests J.R.M. is an inventor on licensed patents and patent applications related to SC islets. J.R.M. was employed at and has stock in Sana Biotechnology. M.I. has stock in Vertex Pharmaceuticals.

PubMed

Coxsackievirus B triggers unique responses in different cell types of human pancreatic islets

Abstract

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Competing interests

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