title: Influenza A viruses grow in human pancreatic cells and cause pancreatitis and diabetes in an animal model.
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 play a role as a causative agent of pancreatitis and diabetes in humans and other mammals.
authors.affiliation: Department of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Padova, Italy. icapua@izsvenezie.it
authors.forename: Ilaria
authors.initials: I
authors.lastname: Capua
authors.forename: Alessia
authors.initials: A
authors.lastname: Mercalli
authors.forename: Matteo S
authors.initials: MS
authors.lastname: Pizzuto
authors.forename: Aurora
authors.initials: A
authors.lastname: Romero-Tejeda
authors.forename: Samantha
authors.initials: S
authors.lastname: Kasloff
authors.forename: Cristian
authors.initials: C
authors.lastname: De Battisti
authors.forename: Francesco
authors.initials: F
authors.lastname: Bonfante
authors.forename: Livia V
authors.initials: LV
authors.lastname: Patrono
authors.forename: Elisa
authors.initials: E
authors.lastname: Vicenzi
authors.forename: Valentina
authors.initials: V
authors.lastname: Zappulli
authors.forename: Vito
authors.initials: V
authors.lastname: Lampasona
authors.forename: Annalisa
authors.initials: A
authors.lastname: Stefani
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.forename: Calogero
authors.initials: C
authors.lastname: Terregino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cattoli
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Piemonti
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D002460:Cell Line; D003920:Diabetes Mellitus / Q000209:etiology / Q000821:virology*; D004195:Disease Models, Animal; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D009980:Influenza A virus / Q000472:pathogenicity*; D050417:Insulin-Secreting Cells / Q000821:virology; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000032:analysis; D010179:Pancreas / Q000473:pathology / Q000821:virology; D010195:Pancreatitis / Q000150:complications* / Q000821:virology*; D017422:Sequence Analysis, DNA; D014422:Turkeys
chemical_list: D000956:Antigens, Viral; D009698:Nucleoproteins