Phenotypic and Genetic Changes in Coxsackievirus B5 Following Repeated Passage in Mouse Pancreas In Vivo

Common enterovirus infections appear to initiate or facilitate the pathogenetic processes leading to type 1 diabetes, and also sometimes precipitate the clinical disease. In experimental infection of mice, coxsackieviruses have shown to have a strong affinity for the exocrine tissue, while even in l...

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Bibliographic Details
Published in:Journal of medical virology 2005-04, Vol.75 (4), p.566-574
Main Authors: Al-Hello, Haider, Davydova, Berta, Smura, Teemu, Kaialainen, Svetlana, Ylipaasto, Petri, Saario, Elise, Hovi, Tapani, Tapani, Elizabeth, Roivainen, Merja
Format: Article
Language:English
Subjects:
amino acid substitution
Animals
Biological and medical sciences
Blood Glucose
Chronic Disease
chronic inflammation
coxsackievirus
diabetogenic viruses
Enterovirus
Enterovirus B, Human - classification
Enterovirus B, Human - genetics
Enterovirus B, Human - pathogenicity
Enterovirus Infections - immunology
Enterovirus Infections - pathology
Enterovirus Infections - physiopathology
Enterovirus Infections - virology
Fundamental and applied biological sciences. Psychology
genetic determinants
genetic variation
Genetics
genome
Genotype
glucose metabolism dysregulation
Human viral diseases
in vivo studies
in vivo virus passage
increased blood glucose
infection
Infectious diseases
Inflammation
Male
Medical sciences
Mice
Microbiology
Miscellaneous
mouse pancreas
pancreas
Pancreas - immunology
Pancreas - pathology
Pancreas - virology
Phenotype
repeated passages
sequence analysis
Serial Passage
serotypes
Viral diseases
Virology
virus replication
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Summary:Common enterovirus infections appear to initiate or facilitate the pathogenetic processes leading to type 1 diabetes, and also sometimes precipitate the clinical disease. In experimental infection of mice, coxsackieviruses have shown to have a strong affinity for the exocrine tissue, while even in lethal cases, the islets remain unaffected. The virus strain most intensively studied in this respect is the diabetogenic variant E2 of coxsackievirus B4. In addition, it is known that all six serotypes of coxsackie B viruses can be made diabetogenic by repeated passages in either mouse pancreas in vivo or in cultured mouse beta-cells in vitro. However, the genetic determinants of the phenomenon have not been determined. In the present study, a laboratory strain of coxsackievirus B5 was passaged repeatedly in mouse pancreas in vivo. After 15 passages, the virus phenotype was clearly changed and infection of the variant resulted in a diabetes-like syndrome in mice characterized by chronic pancreatic inflammation together with dysregulation in glucose metabolism, loss of pancreatic acinar tissue, and mild insulitis. In order to characterize the genetic determinants involved in mouse pancreas adaptation, the passaged virus variant together with the parental virus strain was cloned for molecular characterization. The whole genome sequencing of both virus strains revealed only limited differences. Altogether, eight nucleotides were changed resulting in five amino acid substitutions, of which three were located in the capsid proteins.
ISSN:1096-9071
0146-6615
1096-9071
DOI:10.1002/jmv.20303