Coxsackie B virus infection of mice: inoculation by the oral route protects the pancreas from damage, but not from infection

Shubhada Bopegamage, Jana Kovacova, Agnesa Vargova, Jana Motusova, Anna Petrovicova, Maria Benkovicova, Pavol Gomolcak, Judith Bakkers, Frank van Kuppeveld, Willem J G Melchers, Jochem M Galama

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    The pathogenesis of coxsackie B virus (CVB) infections is generally studied in mice by intraperitoneal (i.p.) injection, whereas the gastrointestinal tract is the natural porte d'entrée in humans. The present study was undertaken to compare systematically the influence of infection route on morbidity and pathology. Swiss Albino mice were infected with CVB3 (Nancy) at different doses (5 x 10(3), 5 x 10(5), 5 x 10(7), 5 x 10(9) TCID50), given either i.p. or orally. Virus could be isolated from several organs (heart, spleen and pancreas), indicating systemic infection, irrespective of the infection route. Virus titres were 1-2 logs higher after i.p. infection, but kinetics were largely independent of infection route. Organs became negative for virus isolation after 21 days, with the exception of spleen tissue, which remained positive for up to 49 days. Thereafter, virus was detected only by immunohistochemistry and PCR up to 98 days post-infection (oral route). Histopathology showed mild inflammation and necrosis in heart tissue of all mice during the acute phase, with repair at later stages. Strikingly, pancreatic lesions were confined to the exocrine pancreas and observed only after i.p. infection. Under all experimental conditions, the pancreatic islets were spared. In contrast, immunohistochemistry showed the presence of viral VP1, protein 3A and alpha interferon (IFN-alpha) in exocrine as well as endocrine pancreas of all mice, irrespective of route and dose of infection. It is concluded that infection via the oral route protects the pancreas from damage, but not from infection, a process in which IFN-alpha is not the only factor involved.

    Original languageEnglish
    Pages (from-to)3271-80
    Number of pages10
    JournalJournal of General Virology
    Volume86
    Issue numberPt 12
    DOIs
    Publication statusPublished - Dec 2005

    Keywords

    • Administration, Oral
    • Animals
    • Cell Line
    • Cercopithecus aethiops
    • Coxsackievirus Infections
    • Disease Models, Animal
    • Enterovirus B, Human
    • Heart
    • Immunohistochemistry
    • Inflammation
    • Injections, Intraperitoneal
    • Interferon-alpha
    • Intestine, Small
    • Mice
    • Mice, Inbred ICR
    • Myocardium
    • Necrosis
    • Pancreas
    • Polymerase Chain Reaction
    • RNA, Viral
    • Spleen
    • Viral Proteins

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