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Scientific Reports Jul 2019Coxsackieviruses B (CV-B) belong to the EV-B species. CV-B and particularly CV-B4 are thought to be involved in the development of chronic diseases like type 1 diabetes...
Coxsackieviruses B (CV-B) belong to the EV-B species. CV-B and particularly CV-B4 are thought to be involved in the development of chronic diseases like type 1 diabetes (T1D). The mechanisms of the enteroviral pathogenesis of T1D are not well known, yet. The in vitro studies are rich with information but in vivo infection models are needed to investigate the impact of viruses onto organs. Our objective was to study the impact of CV-B4E2 combined with a single sub-diabetogenic dose of streptozotocin (STZ) on the pancreas of mice. The infection with CV-B4E2 of CD1 outbred mice treated with a sub-diabetogenic dose of STZ induced hyperglycemia and hypoinsulinemia. Along with the chemokine IP-10, viral RNA and infectious particles were detected in the pancreas. The pancreas of these animals was also marked with insulitis and other histological alterations. The model combining STZ and CV-B4E2 opens the door to new perspectives to better understand the interactions between virus and host, and the role of environmental factors capable, like STZ, to predispose the host to the diabetogenic effects of enteroviruses.
Topics: Animals; Cell Line; Chemokine CXCL10; Coxsackievirus Infections; Diabetes Mellitus, Type 1; Enterovirus B, Human; Host-Pathogen Interactions; Humans; Hyperglycemia; Insulin; Male; Mice; Pancreas; Streptozocin; Viral Load
PubMed: 31300658
DOI: 10.1038/s41598-019-46227-3 -
Archives of Internal Medicine Feb 1975White mice of the NYA: NYLAR strain were infected with coxsackie B1 or B4 virus and studied for persistence of virus, antibody conversion, histologic changes, and...
White mice of the NYA: NYLAR strain were infected with coxsackie B1 or B4 virus and studied for persistence of virus, antibody conversion, histologic changes, and glucose tolerance during periods up to 13 months. Pancreatitis was observed during the acute phase of infection. Suggestions of subclinical diabetes were found during the first six months after virus inoculation. A normal glucose tolerance at 10 to 13 months suggestes that the functional lesion is temporary.
Topics: Animals; Antibody Formation; Blood Glucose; Coxsackievirus Infections; Diabetes Mellitus; Glucose Tolerance Test; Macaca mulatta; Mice; Mice, Inbred Strains; Pancreas; Pancreatitis; Remission, Spontaneous
PubMed: 1147726
DOI: No ID Found -
Emerging Infectious Diseases Dec 2017Wellfleet Bay virus (WFBV), a novel orthomyxovirus in the genus Quaranjavirus, was first isolated in 2006 from carcasses of common eider (Somateria mollissima) during a...
Wellfleet Bay virus (WFBV), a novel orthomyxovirus in the genus Quaranjavirus, was first isolated in 2006 from carcasses of common eider (Somateria mollissima) during a mortality event in Wellfleet Bay (Barnstable County, Massachusetts, USA) and has since been repeatedly isolated during recurrent mortality events in this location. Hepatic, pancreatic, splenic, and intestinal necrosis was observed in dead eiders. We inoculated 6-week-old common eider ducklings with WFBV in an attempt to recreate the naturally occurring disease. Approximately 25% of inoculated eiders had onset of clinical disease and required euthanasia; an additional 18.75% were adversely affected based on net weight loss during the trial. Control ducklings did not become infected and did not have clinical disease. Infected ducklings with clinical disease had pathologic lesions consistent with those observed during natural mortality events. WFBV was reisolated from 37.5% of the inoculated ducklings. Ducklings surviving to 5 days postinoculation developed serum antibody titers to WFBV.
Topics: Animals; Antibodies, Viral; Bays; Bird Diseases; Disease Models, Animal; Ducks; Intestines; Liver; Massachusetts; Necrosis; Orthomyxoviridae; Orthomyxoviridae Infections; Pancreas; Spleen; Weight Loss
PubMed: 28841405
DOI: 10.3201/eid2312.160366 -
Lancet (London, England) Nov 1978
Topics: Bronchitis; Chlorides; Chronic Disease; Cystic Fibrosis; Diagnosis, Differential; Humans; Pancreas; Pseudomonas Infections; Staphylococcal Infections; Sweat
PubMed: 82041
DOI: No ID Found -
Acta Virologica 2003The study was focused on kinetics of Coxsackievirus B3 serotype (CVB3) in different organs of Swiss albino mice following intraperitoneal (i.p.) infection. The results...
The study was focused on kinetics of Coxsackievirus B3 serotype (CVB3) in different organs of Swiss albino mice following intraperitoneal (i.p.) infection. The results indicated that the virus replicated in the heart, spleen, thymus, pancreas, small and large intestines in the acute stage of the infection. Infectious virus was present in the spleen till day 35 post infection (p.i.). Histopathology of the hearts showed mild foci of infiltration of mononuclear cells in the acute stage of infection and massive inflammation of exocrine pancreas on day 5 p.i. These results, when compared to those of our previous study (Bopegamage et al., 2003), suggest that the pathogenesis of the disease may be influenced by the route of virus administration into the host.
Topics: Animals; Antibodies, Viral; Coxsackievirus Infections; Enterovirus B, Human; Injections, Intraperitoneal; Kinetics; Mice; Mice, Inbred ICR; Myocardium; Pancreas; Virus Replication
PubMed: 15068381
DOI: No ID Found -
Anatomical Record (Hoboken, N.J. : 2007) May 2008Some coxsackievirus B serotypes are potentially diabetogenic. Previous studies revealed that the virulence and the tissue damage varied with the genetics of the virus...
Some coxsackievirus B serotypes are potentially diabetogenic. Previous studies revealed that the virulence and the tissue damage varied with the genetics of the virus strain as well as with the genetics of the mice. A single amino acid variation can alter virulence and tropism in both murine and in vitro models. However, the genetic determinants of this phenomenon have not been determined. In this study, infections with a laboratory strain of coxsackievirus B4 resulted in a diabetes-like syndrome in ICR mice, characterized by chronic pancreatic inflammation together with dysregulation in glucose metabolism, loss of pancreatic acinar tissue and persistent infection in islets. To characterize the genetic determinants involved in the mouse pancreas adaptation, the laboratory strain of coxsackievirus B4 was cloned for molecular characterization. Comparing the whole genome sequence of this virus strain with the other coxsackievirus B4 strains revealed some differences. Altogether 15 nucleotides were changed, resulting in 10 amino acid substitutions, which might be responsible for the pathogenic phenotype of this strain in mice.
Topics: Animals; Coxsackievirus Infections; Enterovirus; Genome, Viral; Glucose; Glucose Intolerance; Glucose Metabolism Disorders; Host-Pathogen Interactions; Male; Mice; Mice, Inbred ICR; Pancreas; Phylogeny; Sequence Analysis; Virulence
PubMed: 18384052
DOI: 10.1002/ar.20690 -
Cellular and Molecular Life Sciences :... Nov 2013The role of enteroviruses, especially Coxsackievirus B (CVB), in type 1 diabetes is suspected, but the mechanisms of the virus-induced or aggravated pathogenesis of the...
Coxsackievirus B4 can infect human pancreas ductal cells and persist in ductal-like cell cultures which results in inhibition of Pdx1 expression and disturbed formation of islet-like cell aggregates.
The role of enteroviruses, especially Coxsackievirus B (CVB), in type 1 diabetes is suspected, but the mechanisms of the virus-induced or aggravated pathogenesis of the disease are unknown. The hypothesis of an enterovirus-induced disturbance of pancreatic β-cells regeneration has been investigated in the human system. The infection of human pancreas ductal cells and pancreatic duct cell line, PANC-1, with CVB4E2 has been studied. Primary ductal cells and PANC-1 cells were infectable with CVB4E2 and a RT-PCR assay without extraction displayed that a larger proportion of cells harbored viral RNA than predicted by the detection of the viral capsid protein VP1 by indirect immunofluorescence. The detection of intracellular positive- and negative-strands of enterovirus genomes in cellular extracts by RT-PCR and the presence of infectious particles in supernatant fluids during the 37 weeks of monitoring demonstrated that CVB4E2 could persist in the pancreatic duct cell line. A persistent infection of these cells resulted in an impaired expression of Pdx1, a transcription factor required for the formation of endocrine pancreas, and a disturbed formation of islet-like cell aggregates of which the viability was decreased. These data support the hypothesis of an impact of enteroviruses onto pancreatic ductal cells which are involved in the renewal of pancreatic β-cells.
Topics: Cell Differentiation; Cell Line; Cell Proliferation; DNA Primers; Diabetes Mellitus, Type 2; Enterovirus B, Human; Gene Expression Regulation, Viral; Homeodomain Proteins; Humans; Insulin-Secreting Cells; Microscopy, Fluorescence; Pancreatic Ducts; RNA, Viral; Time Factors; Trans-Activators
PubMed: 23775130
DOI: 10.1007/s00018-013-1383-4 -
Japanese Journal of Infectious Diseases Jan 2017Saffold cardiovirus (SAFV), first identified in a stool sample in 2007, is thought to be associated with respiratory disease and gastroenteritis. On the other hand,...
Saffold cardiovirus (SAFV), first identified in a stool sample in 2007, is thought to be associated with respiratory disease and gastroenteritis. On the other hand, animal experiments suggested that the major viral load, following intraperitoneal inoculation of SAFV in mice, may be detected in the pancreas. However, until now, no cases of SAFV in patients with pancreatitis have been reported. This report presents a unique case in a patient who developed relapsing acute pancreatitis (AP) after hand, foot, and mouth disease, and was suspected to have SAFV-1 infection. A 2-year-old boy was admitted to the hospital because of severe abdominal pain. His serum amylase and lipase levels were elevated. Enhanced computed tomography showed pancreatic swelling and dilation of the main pancreatic duct, leading to a diagnosis of severe AP. The viral genome of SAFV-1 was detected by reverse transcription polymerase chain reaction from fecal samples. Furthermore, the serum neutralization titer for SAFV was elevated during AP, but decreased after 1 year. These findings strongly suggest the patient developed SAFV-1 infection concurrent with AP. Therefore, we propose that a cohort study is required to clarify the relationship between SAFV and AP.
Topics: Amylases; Antibodies, Neutralizing; Antibodies, Viral; Cardiovirus; Cardiovirus Infections; Child, Preschool; Feces; Hand, Foot and Mouth Disease; Humans; Lipase; Male; Pancreas; Pancreatitis, Acute Necrotizing; RNA, Viral; Reverse Transcriptase Polymerase Chain Reaction; Tomography, X-Ray Computed
PubMed: 27000454
DOI: 10.7883/yoken.JJID.2015.488 -
Archives of Virology Jul 2004Mechanistic studies of hantavirus persistence in rodent reservoirs have been limited by the lack of a versatile animal model. This report describes findings from...
Mechanistic studies of hantavirus persistence in rodent reservoirs have been limited by the lack of a versatile animal model. This report describes findings from experimental infection of inbred Lewis rats with Seoul virus strain 80-39. Rats inoculated with virus intraperitoneally at 6 days of age became persistently infected without clinical signs. Tissues from Seoul virus-inoculated 6-day-old rats were assessed at 6, 9, and 12 weeks post-inoculation for viral RNA by RT-PCR and in situ hybridization (ISH) and for infectious virus by inoculation of Vero E6 cells. Virus was isolated from lung and kidney of infected rats at 6 weeks and viral RNA was detected in lung, kidney, pancreas, salivary gland, brain, spleen, liver and skin at 6, 9 and 12 weeks. Rats inoculated with Seoul virus intraperitoneally at 10 or 21 days of age became infected without clinical signs but had low to undetectable levels of viral RNA in tissues at 6 weeks post-inoculation. ISH identified vascular smooth muscle and endothelial cells as common sites of persistent infection. Cultured rat smooth muscle cells and to a lesser extent cultured endothelial cells also were susceptible to Seoul virus infection. Pancreatic infection resulted in insulitis with associated hyperglycemia. These studies demonstrate that infant Lewis rats are uniformly susceptible to asymptomatic persistent Seoul virus infection. Additionally, they offer opportunities for correlative in vivo and in vitro study of Seoul virus interactions in host cell types that support persistent infection.
Topics: Animals; Antibodies, Viral; Brain; Cells, Cultured; Disease Reservoirs; Endothelial Cells; Hantavirus Infections; Hemorrhagic Fever with Renal Syndrome; Hyperglycemia; In Situ Hybridization; Islets of Langerhans; Kidney; Liver; Lung; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Pancreas; RNA, Viral; Rats; Rats, Inbred Lew; Reverse Transcriptase Polymerase Chain Reaction; Salivary Glands; Seoul virus; Skin; Spleen
PubMed: 15221534
DOI: 10.1007/s00705-004-0294-y -
Liver Feb 1991One hundred and seventeen ducklings, 42 inoculated with duck hepatitis B virus (DHBV) 2 days after hatching and 55 connatally infected, were studied over a 6-month...
One hundred and seventeen ducklings, 42 inoculated with duck hepatitis B virus (DHBV) 2 days after hatching and 55 connatally infected, were studied over a 6-month period in parallel with 20 ducklings without DHBV infection. Using immunohistochemical, in situ and blot hybridization analyses, the natural course of hepatic and extrahepatic infection was examined. DHBV infection started in the liver 2-4 days post-inoculation. There, DHBV was found not only in hepatocytes, but also in bile duct epithelial cells. Further, DHBV infection occurred in exocrine and endocrine pancreas (beginning 6-10 days and 20 days post-inoculation, respectively) and in germinal centers of the spleen (beginning 8 weeks post-inoculation). Occasionally viral DNA was also found in kidney glomeruli. Using strand-specific RNA probes, viral DNA in pancreas and spleen was clearly demonstrated to be replicating intermediates. Hepatic and extrahepatic infection with DHBV was not associated with histologic inflammation or pathologic changes in these tissues or the liver. These data indicate that DHBV can infect cells other than hepatocytes. The biological significance of non-hepatocyte infection for the life-cycle of the virus and its potential significance for viral persistence remain to be determined.
Topics: Animals; Bile Ducts; Bird Diseases; Blotting, Southern; Ducks; Hepatitis B Virus, Duck; Hepatitis, Viral, Animal; Kidney Glomerulus; Pancreas; RNA Probes; Spleen
PubMed: 2046495
DOI: 10.1111/j.1600-0676.1991.tb00491.x