The pathology of murine coxsackievirus B3 myocarditis: An in situ hybridization study

Shigehiro Sato, Allen P. Burke, William Benson, Wolfgang Mergner, Steven Tracy, Charles Gauntt, Renu Virmani

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Abstract

Histologic changes and localization of viral RNA synthesis were studied in cardiac sections of outbred immunocompetent (CD-1) and athymic (nude) Swiss mice infected with a myocardiac variant of coxsackievirus B3 (CVB3). Viral effects in heart tissue sections progressed through four phases in both models. The first phase consisted of histologically normal myocardium with scattered myocytes which were strongly positive for nascent viral RNA by in situ hybridization using a negative strand CVB3 RNA probe. These cells often appeared in clusters. The second phase consisted of focal myocarditic lesions with histologic changes of cell necrosis with accompanying lymphocytes and histiocytes; the in situ hybridization signal was moderate at this stage. Phase 3 demonstrated relatively large lesions with inflammatory infiltrate without recognizable myocyte cytoplasm; these lesions showed a weak hybridization signal. Healed (phase 4) lesions were negative for viral RNA by in situ hybridization and histologically were composed of fibroblast infiltrates with a sparse histiocyte infiltrate. RNA sequences from the enteroviral VP-1 region were detectable by polymerase chain reaction in phases 1 through 3 and some phase 4 lesions in both models. Although the time course of lesion formation was different, lesion development progressed through similar recognizable phasesin both murine models. There is an intimate association between presence of virus and myocarditis lesions in two diverse murine models, indicating that the mechanism of lesion formation is most likely a cytopathic viral effect and not an autoimmune phenomenon. The lack of hybridization signal over healed lesions is most likely attributable to lack of sensitivity of the procedure.

Original languageEnglish (US)
Pages (from-to)107-115
Number of pages9
JournalCardiovascular Pathology
Volume2
Issue number2
DOIs
StatePublished - 1993

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cardiology and Cardiovascular Medicine

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    Sato, S., Burke, A. P., Benson, W., Mergner, W., Tracy, S., Gauntt, C., & Virmani, R. (1993). The pathology of murine coxsackievirus B3 myocarditis: An in situ hybridization study. Cardiovascular Pathology, 2(2), 107-115. https://doi.org/10.1016/1054-8807(93)90022-T