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European Heart Journal 2002 23(7):567-573; doi:10.1053/euhj.2001.2837
Copyright © 2002 by the European Society of Cardiology.
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Enterovirus replication in valvular tissue from patients with chronic rheumatic heart disease

Y Lia, Z Panb, Y Jib, T Penga, L.C Archarda and H Zhanga,f1

a Cell and Molecular Biology Section, Division of Biomedical Sciences, Imperial College School of Medicine, London, U.K.
b Departments of General Practice and Pathology, Zhongshan Hospital, Shanghai Medical University, Shanghai, P. R. China

revised June 15, 2001; accepted June 20, 2001

Abstract

Aims To investigate the involvement of enterovirus infection in chronic, rheumatic heart disease.

Methods and Results Formalin-fixed, paraffin-embedded, surgical samples of valve tissue were examined for the presence of enteroviral RNA and virus capsid protein VP1 by in situ hybridization and immunostaining. Of 53 cases, 33 were patients with chronic rheumatic heart disease and 20 had Marfan's syndrome or degenerative valve disease. Enterovirus RNA was detected in 8 (24·2%) of 33 patients with chronic rheumatic heart disease by in situ hybridization using strand-specific oligonucleotide probes, complementary to conserved sequences in enterovirus genomic (positive strand) RNA. The replication template (negative strand) RNA also was found in seven of these eight cases. The viral capsid protein VP1 was detected in 16 (48·5%) of 33 patients with chronic rheumatic heart disease by immunohistochemistry and correlated with viral RNA detection. Virus was localized generally to valvular tissue. Neither viral RNA nor capsid protein VP1 were found in valvular tissue from any of the 20 comparison cases.

Conclusions This is the first demonstration of detection and localization of both enterovirus RNA and capsid protein in chronic rheumatic heart disease. The presence of negative strand RNA and VP1 indicates enteroviral RNA replication and protein synthesis and suggests an aetiological role of enterovirus in the pathogenesis of chronic rheumatic heart disease.

Key Words: Rheumatic heart disease, valves, enteroviruses, hybridization, immunohistochemistry

f1 Correspondence: Dr. Hongyi Zhang, Cell and Molecular Biology Section, Division of Biomedical Sciences, Sir Alexander Fleming Building, Imperial College School of Medicine, Exhibition Road, London SW7 2AZ, U.K.

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