A Preliminary Analysis of Hepatitis C Virus in Pancreatic Islet Cells

Virol J. 2017 Dec 20;14(1):237. doi: 10.1186/s12985-017-0905-3.

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. Positive- and 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: Diabetes; Extrahepatic replication; Hepatitis C virus; Islet cells; Pancreas.

MeSH terms

  • Antiviral Agents / pharmacology
  • Cells, Cultured
  • Cytokines / metabolism
  • HEK293 Cells
  • Hepacivirus / drug effects
  • Hepacivirus / physiology*
  • Hepatitis C / blood
  • Hepatitis C / virology*
  • Hepatocytes
  • Humans
  • Interferon-alpha / pharmacology
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / virology*
  • MicroRNAs / metabolism
  • RNA, Viral
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sofosbuvir / pharmacology
  • Viral Nonstructural Proteins / metabolism
  • Virion / physiology
  • Virus Internalization
  • Virus Replication / drug effects
  • Virus Replication / physiology

Substances

  • Antiviral Agents
  • Cytokines
  • Interferon-alpha
  • MIRN122 microRNA, human
  • MicroRNAs
  • NS3 protein, hepatitis C virus
  • RNA, Viral
  • Viral Nonstructural Proteins
  • Sofosbuvir