No evidence for persistent enteroviral B infection of pancreatic islets in type 1 diabetic and pre-diabetic patients from RNA-Seq data

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posted on 2024-07-26, 18:13 authored by Elisabetta Manduchi, Hélène C. Descamps, Jonathan Schug, Tong Da, Deeksha Lahori, Hilana El-Mekkoussi, Michael R. Betts, Klaus H. Kaestner

Abstract

Persistent enterovirus B infection has been proposed as an important contributor to the etiology of type 1 diabetes. We leveraged extensive bulk RNA-sequencing data from alpha, beta, and exocrine cells, as well as single cell islet RNA-Seq data from the Human Pancreas Analysis Program (HPAP), to evaluate the presence of enterovirus B sequences in the pancreas of type 1 diabetic and pre-diabetic (non-diabetic but auto-antibody positive) patients. We examined all available HPAP data for either assay type, including non-diabetic, type 1, and type 2 diabetic donors. To assess the presence of viral reads, we analyzed all reads not mapping to the human genome with the taxonomic classification system Kraken2 and its full viral database, augmented to encompass representatives for all (28) enterovirus B serotypes for which a complete genome is available. As a secondary approach, we input the same sequence reads into the STAR aligner using these 28 enterovirus B genomes as the reference. No enterovirus B sequences were detected by either approach in any of the 243 bulk RNA libraries nor in any of the 79 single cell RNA libraries. While we cannot rule out the possibility of a very low-grade persistent enterovirus B infection in the donors analyzed, our data do not support the notion of chronic viral infection by these viruses as a major driver of type 1 diabetes.

Keywords: type 1 diabetes, enterovirus B, persistent viral infection, RNA-Seq

Article Highlights

• Persistent enterovirus B infections of pancreatic islets have been suggested as trigger for autoimmunity leading to type 1 diabetes in genetically susceptible individuals.

• Unbiased sequence-based analysis of bulk and single cell RNA-Seq data from the Human Pancreas Analysis Program found no evidence for presence of enterovirus B sequences in the human pancreas.

• While our findings do not rule out the possibility of a very low-grade persistent enterovirus B infection, our data do not support the notion of chronic viral infection by these viruses.