End-stage dilated cardiomyopathy. Persistence of enterovirus RNA in myocardium at cardiac transplantation and lack of immune response.

Abstract

(Circulation 1989;80:1128-1136

Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA

“…In some patients where enteroviral RNA can be demonstrated in the affected tissue, a continuing humoral immune response against normal viral antigens cannot be detected (Archard et al, 1988;Bowles et al, 1989). This, together with the documented failure to isolate infectious virus or detect virus-specific antigens, suggests that the progression to chronic disease is associated with the selection of defective virus.…”

“…In this way, probes complementary to either virus genomic (positive strand) RNA or template (negative strand) RNA could be synthesized by in vitro transcription by SP6 RNA polymerase. The nucleotide sequence of the RNAdependent RNA polymerase is highly conserved between enterovirus serotypes (Stalhandske et al, 1984) and so probes derived from this region are enterovirus group-specific (Bowles et al, 1989). 32p-labeUed RNA probes were synthesized by transcription of linearized template DNA according to standard protocols (Promega Biotec).…”

“…Doubling dilutions of RNA extracted from normal muscle were blotted and probed with 7B6-specific riboprobe to establish that the autoradiographic signal obtained is proportional to the amount of RNA blotted. Autoradiographic development was quantified by scanning densitometry and the integrals under peaks were plotted as a function of RNA concentration; a linear relationship was obtained (Bowles et al, 1989). Subconfluent monolayers of LLCMK: cells (rhesus monkey kidney) were infected with CVB2 at 105 or 104 p.f.u./ml or mock-infected.…”

Clinical Significance of Viral Genome Persistence in the Myocardium of Patients with Dilated Cardiomyopathy

“…Accordingly, patients with viral genomes and high incidence of active myocarditis or immunohistology-proven inflammatory response were predisposed to poor prognosis [17,18] . Conversely, a lack of concomitant inflammatory response in the myocardium with a viral presence was not related to poor outcome [5,19] . Secondly, not the virus presence per se but the phase of such presence (replication and lysogenic) in the myocardium seems to be a main predictor of poorer clinical outcomes.…”

Cellular and biomolecular mechanisms in dilated cardiomyopathy

“…The advent of new techniques of molecular biology based upon nucleic acid hybridization, made enteroviral RNA detection possible in up to 43% and 47% of the samples containing myocardial tissue of patients with DCM and myocarditis, respectively 13,14 . Later determinations using the polymerase chain reaction (PCR) technique, more sensitive and specific, observed the presence of enteroviral genomes in 0% to 67% of the biopsies evaluated [15][16][17][18][19] .…”