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Updated: Apr 25, 2026

Assessing Replication and Beta Cell Function in Adenovirally-transduced Isolated Rodent Islets
Published on: June 25, 2012
Kilham Rat Virus-induced type 1 diabetes involves beta cell infection and intra-islet JAK-STAT activation prior to
Aimon K Alkanani1, Naoko Hara1, Roberto Gianani1
1Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, 1775 Aurora Ct., Mail Stop B-140, Aurora, CO 80045, United States.
Abstract:
We used the LEW1.WR1 rat model of Kilham Rat Virus (KRV)-induced type 1 diabetes (T1D) to test the hypothesis that disease mechanisms are linked with beta cell infection and intra-islet immune activation prior to insulitis. KRV induces genes involved in type I and type II interferon pathways in islet cell lines in vitro and in islets from day-5-infected animals in vivo via mechanisms that do not involve insulitis, beta cell apoptosis, or impaired insulin expression. Immunohistochemistry studies indicated that KRV protein is expressed in beta cells 5 days following infection. KRV induces the phosphorylation of Janus Kinase 1/2 (JAK1/2) and signal transducer and activator of transcription 1 (STAT-1) in islet cells via a mechanism that could involve TLR9 and NF-κB pathways. These data demonstrate for the first time that KRV-induced islet destruction is associated with beta cell infection and intra-islet innate immune upregulation early in the disease process.
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