A preliminary analysis of hepatitis C virus in pancreatic islet cells
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RESEARCH
Open Access
A preliminary analysis of hepatitis C virus in pancreatic islet cells Jason T. Blackard1* , Ling Kong1, Angela Lombardi2, Dirk Homann3, Sara Salehi Hammerstad4 and Yaron Tomer2
Abstract Background: An association between hepatitis C virus (HCV) and type 2 diabetes (T2D) is supported by numerous epidemiologic studies. We hypothesized that HCV could infect human pancreatic islet cells in vitro. Methods: Measures of HCV RNA synthesis and protein production were used to evaluate HCV infection of pancreatic islets recovered from human donors. Results: Significant co-staining of insulin and the HCV entry factor CD81 was observed in pancreatic islets. Positiveand negative-sense HCV RNA were detected in HCV-exposed islets at days 1, 3, 7, and 14 post-infection. The HCV core and NS3 proteins were expressed and increased with time providing further evidence of viral replication. Interferon and an HCV polymerase inhibitor reduced viral replication in islet cells. In HCV-infected islets, TNFα levels were elevated at days 1, 3, and 7 post-infection, while IL-6 levels were elevated at day 1 but not days 3 or 7. Overall, the expression of miR-122 was low in islets compared to the Huh7.5 hepatocyte-derived cell line, although the relative expression of miR-122 increased in islet cells after viral infection (1, 6.63, and 5.83 at days 1, 3, and 7, respectively). Conclusions: In this pilot study, viral infection was demonstrated in pancreatic islet cells from multiple donors using complementary measures of viral replication, thus providing evidence of in vitro infection. Altered cytokine expression may contribute to the development of insulin deficiency, and understanding the etiology of diabetes in individuals with HCV infection may facilitate the development of novel treatment modalities and prevention strategies. This in vitro system provides an important model for mechanistic studies of HCV-pancreas interactions and facilitates future studies of the potential impact of viral infection on islet cell function. Keywords: Hepatitis C virus, Pancreas, Islet cells, Extrahepatic replication, Diabetes
Background Over 1.9 billion adults worldwide are overweight and >600 million are obese, corresponding to 39% and 13 of world’s adult population, respectively [1]. Multiple genetic and dietary factors are associated with the development of type 2 diabetes (T2D), although less is know about the role of certain environmental factors such as viral infection. Globally, 130–170 million people are infected with hepatitis C virus (HCV) [2]. While hepatocytes represent the major site of viral replication, liver disease is not the sole outcome of HCV replication, and extrahepatic complications of HCV infection are common and complicate its management (reviewed in [3]). * Correspondence: [email protected] 1 Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, ML 0595, 231 Albert Sabin Way, Cincinnati, OH 45267, USA Full list of author information is available at the
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