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

Lab Invest. 1992 Jan;66(1):24-31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • Cardiomyopathies / etiology*
  • Cardiomyopathies / immunology
  • Cardiomyopathies / microbiology
  • Coxsackievirus Infections / complications
  • DNA, Viral / analysis
  • Disease Models, Animal
  • Enterovirus B, Human / immunology
  • Enterovirus B, Human / isolation & purification
  • Enterovirus Infections / complications*
  • Enterovirus Infections / immunology
  • Heart / microbiology
  • Immunohistochemistry
  • Immunophenotyping
  • Lymphocyte Depletion
  • Macrophages / immunology
  • Major Histocompatibility Complex / immunology
  • Mice
  • Mice, Inbred C3H
  • Mice, SCID / microbiology*
  • Myocarditis / etiology
  • Myocarditis / immunology
  • Myocarditis / microbiology
  • Myocardium / pathology
  • Necrosis
  • Nucleic Acid Hybridization
  • Severe Combined Immunodeficiency / complications*
  • Severe Combined Immunodeficiency / immunology
  • Virus Replication

Substances

  • Antigens, Viral
  • DNA, Viral