A. Heim et al., ENTEROVIRUS HEART-DISEASE OF ADULTS - A PERSISTENT, LIMITED ORGAN INFECTION IN THE PRESENCE OF NEUTRALIZING ANTIBODIES, Journal of medical virology, 53(3), 1997, pp. 196-204
Detection of enterovirus RNA in endomyocardial biopsies (EMB) by rever
se transcription! polymerase chain reaction (RT-PCR) is currently the
preferred diagnostic procedure in suspected enterovirus heart disease
(EHD), which can present clinically as myocarditis, dilated cardiomyop
athy (DCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC)
. EMB and peripheral blood mononuclear cells (PBMC) of 44 patients wit
h suspected EHD were examined by nested RT-PCR to investigate whether
the myocardial enterovirus infection is limited to the heart or is gen
eralized. Enterovirus RNA was detected in EMB, but not in PBMC, of 8 p
atients (3 of these suffered from ARVC), whereas EMB of 16 controls an
d PBMC of 45 controls were negative. In addition, enterovirus RNA was
demonstrated in PBMC, but not in EMB, of a single patient with suspect
ed EHD. A high sequence homology of the amplicons to coxsackievirus B3
was demonstrated in 7 patients, and to coxsackievirus B2 in two patie
nts. In order to evaluate whether the myocardial enterovirus infection
was acute or persistent, neutralization and complement fixation tests
were performed for antibodies against the serotypes indicated by the
nucleic acid sequences. Neutralizing antibodies were detected in the s
era of all 9 patients, but complement fixing antibodies were demonstra
ted only in one EHD patient and in the patient positive for enteroviru
s RNA in PBMC. In conclusion, the molecular and serological data demon
strate that CVB3 predominates as cardiotropic enterovirus, and that th
e enterovirus replication is limited to the heart in EHD. Serological
results support the hypothesis of myocardial enterovirus RNA persisten
ce in spite of neutralizing antibodies. (C) 1997 Wiley-Liss, Inc.