Enteroviral infection of mice with severe combined immunodeficiency: Evidence for direct viral pathogenesis of myocardial injury

L. H. Chow, K. W. Beisel, B. M. McManus

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

Inbred mice with genetically determined severe combined immunodeficiency (SCID) lack mature T and B lymphocyte functions. To distinguish direct viral effects in the pathogenesis of myocarditis from those mediated by antigen- specific and histocompatibility-complex-restricted host immunity, we inoculated coxsackievirus B3 into homozygous young adult SCID mice. We found that infected SCID mice invariably developed extensive myocarditis between 7 and 14 days postinoculation with high subsequent mortality. Histopathologic examination of the infected SCID myocardium indicated multiple foci of cardiomyocyte necrosis and a delayed pleomorphic inflammatory infiltrate. Immunohistochemically, the coxsackievirus B3-infected SCID heart contained frequent clusters of macrophages (Mac-1+) as well as other cells that may represent nonspecific phagocytic or cytolytic effectors. In situ hybridization with radiolabeled cDNA probes for enteroviral genome indicated a significant excess of positive-strand genome in the SCID myocardium compared with that in similarly infected non-SCID controls, with hybridization signals localized primarily to cardiomyocytes. In vitro culture confirmed persistent viremia and a vast excess of infective virus in the SCID myocardium relative to infected non-SCID controls. Thus, direct viral mechanisms in the production of cardiomyocyte injury in coxsackievirus B3- infected mice appear to be more important than previously recognized, particularly in the setting of unrestricted viral proliferation.

Original languageEnglish (US)
Pages (from-to)24-31
Number of pages8
JournalLaboratory Investigation
Volume66
Issue number1
StatePublished - Jan 1 1992
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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