Study of 2009 H1N1 Pandemic Influenza Virus as a Possible Causative Agent of Diabetes

• Published in: The journal of clinical endocrinology and metabolism Vol. 103; no. 12; pp. 4343 - 4356
• Main Authors: Capua, Ilaria, Mercalli, Alessia, Romero-Tejeda, Aurora, Pizzuto, Matteo S, Kasloff, Samantha, Sordi, Valeria, Marzinotto, Ilaria, Lampasona, Vito, Vicenzi, Elisa, De Battisti, Cristian, Bonfanti, Riccardo, Rigamonti, Andrea, Terregino, Calogero, Doglioni, Claudio, Cattoli, Giovanni, Piemonti, Lorenzo
• Format: Journal Article
• Language: English
• Published: United States Copyright Oxford University Press 01.12.2018; Oxford University Press
• Subjects: Adolescent; Adult; Animals; Autoimmunity; Beta cells; Blood Glucose; Cell culture; Cell Line; Cell Line, Tumor; Chemokine CXCL10 - immunology; Chemokine CXCL10 - metabolism; Child; Child, Preschool; CXCL10 protein; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - immunology; Diabetes Mellitus, Experimental - virology; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - virology; Dogs; Etiology; Female; Glucose metabolism; Humans; Inflammation; Influenza; Influenza A; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H1N1 Subtype - isolation & purification; Influenza, Human - epidemiology; Influenza, Human - immunology; Influenza, Human - virology; Insulin-Secreting Cells - immunology; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - virology; Localization; Madin Darby Canine Kidney Cells; Male; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Organ donors; Pancreas; Pandemics; Primary Cell Culture; Ribonucleic acid; RNA; RNA, Viral - isolation & purification; Viruses; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2018-00862

Recent studies have suggested that influenza A virus (IAV) might be involved in the etiology of diabetes. To address this question, we tested the ability of H1N1 pandemic IAV to infect, replicate, and damage human β cells/pancreatic islets in vitro and induce pancreatic damage and/or glucose metabolism alterations in chemical and autoimmune models of β cell damage in vivo. Moreover, we looked for direct and/or indirect evidence of correlation between IAV infection and autoimmunity/diabetes in humans. Human H1N1 A/California/2009-derived viruses infected human pancreatic islets in vitro, inducing a proinflammatory response associated with substantial increases of CXCL9 and CXCL10 release. In vivo, infected mice showed a clear susceptibility to the virus, with its localization also found in extrapulmonary organs, including the pancreas. Infection was able to induce mild modifications of glycemia in C57B6 mice after chemical damage of islets but did not modulate the autoimmune damage of islets in NOD mice. One of 69 nasopharyngeal swabs collected from patients at the onset of type 1 diabetes yielded positive results for IAV. Pancreas sections from 17 organ donors available from the Network for Pancreatic Organ Donors With Diabetes showed the persistence of CXCL10-positive cells in islet autoimmunity-positive subjects; however, extremely rare cells stained for viral RNA and not preferentially in autoimmune subjects. Influenza H1N1 pdm strains are able to infect and replicate in mammalian pancreatic cells both in vitro and in vivo but did not cause any functional impairment consistent with diabetes.