Influenza A viruses grow in human pancreatic cells and cause pancreatitis and diabetes in an animal model

Ilaria Capua, Alessia Mercalli, Matteo S. Pizzuto, Aurora Romero-Tejeda, Samantha Kasloff, Cristian De Battisti, Francesco Bonfante, Livia V. Patrono, Elisa Vicenzi, Valentina Zappulli, Vito Lampasona, Annalisa Stefani, Claudio Doglioni, Calogero Terregino, Giovanni Cattoli, Lorenzo Piemonti

Research output: Contribution to journalArticle

Abstract

Influenza A viruses commonly cause pancreatitis in naturally and experimentally infected animals. In this study, we report the results of in vivo investigations carried out to establish whether influenza virus infection could cause metabolic disorders linked to pancreatic infection. In addition, in vitro tests in human pancreatic islets and in human pancreatic cell lines were performed to evaluate viral growth and cell damage.Infection of an avian model with two low-pathogenicity avian influenza isolates caused pancreatic damage resulting in hyperlipasemia in over 50% of subjects, which evolved into hyperglycemia and subsequently diabetes.Histopathology of the pancreas showed signs of an acute infection resulting in severe fibrosis and disruption of the structure of the organ. Influenza virus nucleoprotein was detected by immunohistochemistry (IHC) in the acinar tissue. Human seasonal H1N1 and H3N2 viruses and avian H7N1 and H7N3 influenza virus isolates were able to infect a selection of human pancreatic cell lines. Human viruses were also shown to be able to infect human pancreatic islets. In situ hybridization assays indicated that viral nucleoprotein could be detected in beta cells. The cytokine activation profile indicated a significant increase of MIG/CXCL9, IP-10/CXCL10, RANTES/CCL5, MIP1b/CCL4, Groa/CXCL1, interleukin 8 (IL-8)/CXCL8, tumor necrosis factor alpha (TNF-α), and IL-6. Our findings indicate that influenza virus infection may playarole as a causative agent of pancreatitis and diabetes in humans and other mammals.

Original languageEnglish
Pages (from-to)597-610
Number of pages14
JournalJournal of Virology
Volume87
Issue number1
DOIs
Publication statusPublished - Jan 2013

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pancreatitis
Influenza A virus
Pancreatitis
diabetes
Animal Models
animal models
Orthomyxoviridae
nucleoproteins
infection
islets of Langerhans
cells
Nucleoproteins
Virus Diseases
Islets of Langerhans
H7N3 Subtype Influenza A Virus
cell lines
vertebrate viruses
Infection
H3N2 Subtype Influenza A Virus
interleukin-8

ASJC Scopus subject areas

  • Immunology
  • Virology

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Influenza A viruses grow in human pancreatic cells and cause pancreatitis and diabetes in an animal model. / Capua, Ilaria; Mercalli, Alessia; Pizzuto, Matteo S.; Romero-Tejeda, Aurora; Kasloff, Samantha; De Battisti, Cristian; Bonfante, Francesco; Patrono, Livia V.; Vicenzi, Elisa; Zappulli, Valentina; Lampasona, Vito; Stefani, Annalisa; Doglioni, Claudio; Terregino, Calogero; Cattoli, Giovanni; Piemonti, Lorenzo.

In: Journal of Virology, Vol. 87, No. 1, 01.2013, p. 597-610.

Research output: Contribution to journalArticle

Capua, I, Mercalli, A, Pizzuto, MS, Romero-Tejeda, A, Kasloff, S, De Battisti, C, Bonfante, F, Patrono, LV, Vicenzi, E, Zappulli, V, Lampasona, V, Stefani, A, Doglioni, C, Terregino, C, Cattoli, G & Piemonti, L 2013, 'Influenza A viruses grow in human pancreatic cells and cause pancreatitis and diabetes in an animal model', Journal of Virology, vol. 87, no. 1, pp. 597-610. https://doi.org/10.1128/JVI.00714-12
Capua I, Mercalli A, Pizzuto MS, Romero-Tejeda A, Kasloff S, De Battisti C et al. Influenza A viruses grow in human pancreatic cells and cause pancreatitis and diabetes in an animal model. Journal of Virology. 2013 Jan;87(1):597-610. https://doi.org/10.1128/JVI.00714-12
Capua, Ilaria ; Mercalli, Alessia ; Pizzuto, Matteo S. ; Romero-Tejeda, Aurora ; Kasloff, Samantha ; De Battisti, Cristian ; Bonfante, Francesco ; Patrono, Livia V. ; Vicenzi, Elisa ; Zappulli, Valentina ; Lampasona, Vito ; Stefani, Annalisa ; Doglioni, Claudio ; Terregino, Calogero ; Cattoli, Giovanni ; Piemonti, Lorenzo. / Influenza A viruses grow in human pancreatic cells and cause pancreatitis and diabetes in an animal model. In: Journal of Virology. 2013 ; Vol. 87, No. 1. pp. 597-610.
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AU - Stefani, Annalisa

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