Pathology of the swine-origin influenza A (H1N1) flu

Calore, Edenilson Eduardo; Uip, David Éverson; Perez, Nilda Maria

doi:10.1016/j.prp.2010.11.003

Cited by 40 publications

(44 citation statements)

References 18 publications

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“…Consistent with the autopsies of H 1 N 1 -infected patients, which have documented platelets in the affected lungs, [33][34][35] we observed an accumulation of platelets in bronchoalveolar lavages of H 1 N 1 -infected mice (supplemental Figure 3). The interaction between platelets and H 1 N 1 may thus take place in blood during viremia in critically ill patients or in the inflamed lungs where immune complexes against H 1 N 1 are present, 23 when vascular permeability is increased 65 and/or when the integrity of lung capillaries is compromised.…”

Section: Discussionsupporting

confidence: 88%

“…Platelets are an important source of inflammatory mediators, which are either stored or can be produced de novo upon activation. 3,4 Intrigued by the presence of activated platelets in the blood of critically ill influenza H 1 N 1 infected patients, [33][34][35]37 we aimed to study the activation of platelets by the H 1 N 1 IAV.…”

Section: Discussionmentioning

confidence: 99%

“…17 Indeed, the autopsy of patients with fatal influenza infection revealed pulmonary vascular thrombosis. [33][34][35] Previous work indicating that incubation of human platelets with H 3 N 2 virus induces antibody-and complementdependent platelet lysis could also possibly explain the thrombocytopenia observed in patients. 36 Alternatively, the lower platelet count in IAV-infected patients might result from the direct or indirect platelet activation by the virus, promoting platelet-leukocyte aggregation.…”

Section: Introductionmentioning

confidence: 99%

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Influenza virus H1N1 activates platelets through FcγRIIA signaling and thrombin generation

Boilard

Paré

Rousseau

et al. 2014

Blood

179

177

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Influenza virus H1N1 activates platelets through FcγRIIA signaling and thrombin generation

Boilard

Paré

Rousseau

et al. 2014

Blood

179

177

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“…Necrosis of the pancreatic ductal epithelium was observed in ferrets intragastrically infected with HP H5N1 virus (30), and pancreatic postmortem lesions ranging from inflammation to necrosis have also been observed in HP-IAV-infected cats (31,32). Pathological examinations of human fatalities from the H1N1 2009 pandemic also revealed pancreatic lesions in two of six postmortem examinations (33), and in our recent studies using in vitro and ex vivo models, we demonstrated that human cells originating from the exocrine pancreas were infected and killed by LP IAVs (34). Therefore, although the pancreas is not considered a typical site of replication after standard infection, influenza A virus seems to be capable of infecting and damaging pancreatic cells in severe infections.…”

mentioning

confidence: 87%

Oncolytic Activity of Avian Influenza Virus in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Kasloff

Pizzuto

Silic-Benussi

et al. 2014

J Virol

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Pancreatic ductal adenocarcinoma (PDA) is the most lethal form of human cancer, with dismal survival rates due to late-stage diagnoses and a lack of efficacious therapies. Building on the observation that avian influenza A viruses (IAVs) have a tropism for the pancreas in vivo, the present study was aimed at testing the efficacy of IAVs as oncolytic agents for killing human PDA cell lines. Receptor characterization confirmed that human PDA cell lines express the alpha-2,3-and the alpha-2,6-linked glycan receptor for avian and human IAVs, respectively. PDA cell lines were sensitive to infection by human and avian IAV isolates, which is consistent with this finding. Growth kinetic experiments showed preferential virus replication in PDA cells over that in a nontransformed pancreatic ductal cell line. Finally, at early time points posttreatment, infection with IAVs caused higher levels of apoptosis in PDA cells than gemcitabine and cisplatin, which are the cornerstone of current therapies for PDA. In the BxPC-3 PDA cell line, apoptosis resulted from the engagement of the intrinsic mitochondrial pathway. Importantly, IAVs did not induce apoptosis in nontransformed pancreatic ductal HPDE6 cells. Using a model based on the growth of a PDA cell line as a xenograft in SCID mice, we also show that a slightly pathogenic avian IAV significantly inhibited tumor growth following intratumoral injection. Taken together, these results are the first to suggest that IAVs may hold promise as future agents of oncolytic virotherapy against pancreatic ductal adenocarcinomas. IMPORTANCEDespite intensive studies aimed at designing new therapeutic approaches, PDA still retains the most dismal prognosis among human cancers. In the present study, we provide the first evidence indicating that avian IAVs of low pathogenicity display a tropism for human PDA cells, resulting in viral RNA replication and a potent induction of apoptosis in vitro and antitumor effects in vivo. These results suggest that slightly pathogenic IAVs may prove to be effective for oncolytic virotherapy of PDA and provide grounds for further studies to develop specific and targeted viruses, with the aim of testing their efficacy in clinical contexts.

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“…Previous studies have reported that certain IAVs can also cause pancreatitis in mammals following natural or experimental infection (15)(16)(17)(18). Recently, there have been reports of pancreatic damage in human cases associated with H1N1pdm influenza A virus infection, including both acute pancreatitis and the onset of type 1 diabetes (T1D) (19)(20)(21)(22)(23).…”

mentioning

confidence: 99%

Influenza A Viruses Grow in Human Pancreatic Cells and Cause Pancreatitis and Diabetes in an Animal Model

Capua

Mercalli²,

Pizzuto

et al. 2013

J Virol

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g 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-␣), 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.

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Pathology of the swine-origin influenza A (H1N1) flu

Cited by 40 publications

References 18 publications

Influenza virus H1N1 activates platelets through FcγRIIA signaling and thrombin generation

Influenza virus H1N1 activates platelets through FcγRIIA signaling and thrombin generation

Oncolytic Activity of Avian Influenza Virus in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Influenza A Viruses Grow in Human Pancreatic Cells and Cause Pancreatitis and Diabetes in an Animal Model

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