A preliminary analysis of hepatitis C virus in pancreatic islet cells

Jason T. Blackard, Ling Kong, Angela Lombardi, Dirk Homann, Sara Salehi Hammerstad, Yaron Tomer

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Article number237
JournalVirology Journal
Volume14
Issue number1
DOIs
StatePublished - Dec 20 2017

Fingerprint

Islets of Langerhans
Hepacivirus
Virus Diseases
Infection
RNA
Insulin
Virus Internalization
Type 2 Diabetes Mellitus
Interferons
Epidemiologic Studies
Pancreas
Hepatocytes
Interleukin-6
Staining and Labeling
Cytokines
Cell Line

Keywords

  • Diabetes
  • Extrahepatic replication
  • Hepatitis C virus
  • Islet cells
  • Pancreas

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

A preliminary analysis of hepatitis C virus in pancreatic islet cells. / Blackard, Jason T.; Kong, Ling; Lombardi, Angela; Homann, Dirk; Hammerstad, Sara Salehi; Tomer, Yaron.

In: Virology Journal, Vol. 14, No. 1, 237, 20.12.2017.

Research output: Contribution to journalArticle

Blackard, Jason T. ; Kong, Ling ; Lombardi, Angela ; Homann, Dirk ; Hammerstad, Sara Salehi ; Tomer, Yaron. / A preliminary analysis of hepatitis C virus in pancreatic islet cells. In: Virology Journal. 2017 ; Vol. 14, No. 1.
@article{cc16b3d9f12f4704ab51fc87be3225f5,
title = "A preliminary analysis of hepatitis C virus in pancreatic islet cells",
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",
author = "Blackard, {Jason T.} and Ling Kong and Angela Lombardi and Dirk Homann and Hammerstad, {Sara Salehi} and Yaron Tomer",
year = "2017",
month = "12",
day = "20",
doi = "10.1186/s12985-017-0905-3",
language = "English (US)",
volume = "14",
journal = "Virology Journal",
issn = "1743-422X",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - A preliminary analysis of hepatitis C virus in pancreatic islet cells

AU - Blackard, Jason T.

AU - Kong, Ling

AU - Lombardi, Angela

AU - Homann, Dirk

AU - Hammerstad, Sara Salehi

AU - Tomer, Yaron

PY - 2017/12/20

Y1 - 2017/12/20

N2 - 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.

AB - 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.

KW - Diabetes

KW - Extrahepatic replication

KW - Hepatitis C virus

KW - Islet cells

KW - Pancreas

UR - http://www.scopus.com/inward/record.url?scp=85038444795&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85038444795&partnerID=8YFLogxK

U2 - 10.1186/s12985-017-0905-3

DO - 10.1186/s12985-017-0905-3

M3 - Article

VL - 14

JO - Virology Journal

JF - Virology Journal

SN - 1743-422X

IS - 1

M1 - 237

ER -