A distinct subgroup of cardiomyopathy patients characterized by transcriptionally active cardiotropic erythrovirus and altered cardiac gene expression.
Recent studies have detected erythrovirus genomes in the hearts of cardiomyopathy and cardiac transplant patients. Assessment of the functional status of viruses may provide clinically important information beyond detection of the viral genomes. Here, we report transcriptional activation of cardiotropic erythrovirus to be associated with strongly altered myocardial gene expression in a distinct subgroup of cardiomyopathy patients. Endomyocardial biopsies (EMBs) from 415 consecutive cardiac erythrovirus (B19V)-positive patients with clinically suspected cardiomyopathy were screened for virus-encoded VP1/VP2 mRNA indicating transcriptional activation of the virus, and correlated with cardiac host gene expression patterns in transcriptionally active versus latent infections, and in virus-free control hearts. Transcriptional activity was detected in baseline biopsies of only 66/415 patients (15.9 %) harbouring erythrovirus. At the molecular level, significant differences between cardiac B19V-positive patients with transcriptionally active versus latent virus were revealed by expression profiling of EMBs. Importantly, latent B19V infection was indistinguishable from controls. Genes involved encode proteins of antiviral immune response, B19V receptor complex, and mitochondrial energy metabolism. Thus, functional mapping of erythrovirus allows definition of a subgroup of B19V-infected cardiomyopathy patients characterized by virus-encoded VP1/VP2 transcripts and anomalous host myocardial transcriptomes. Cardiac B19V reactivation from latency, as reported here for the first time, is a key factor required for erythrovirus to induce altered cardiac gene expression in a subgroup of cardiomyopathy patients. Virus genome detection is insufficient to assess pathogenic potential, but additional transcriptional mapping should be incorporated into future pathogenetic and therapeutic studies both in cardiology and transplantation medicine.
Department of Cardiology and Pneumology, Charité Centrum 11 (Cardiovascular Medicine), Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
U
U
Kuhl
D
D
Lassner
A
A
Dorner
M
M
Rohde
F
F
Escher
B
B
Seeberg
E
E
Hertel
C
C
Tschope
C
C
Skurk
U M
UM
Gross
H-P
HP
Schultheiss
W
W
Poller
D009202:Cardiomyopathies / Q000150:complications / Q000235:genetics* / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010322:Parvoviridae Infections / Q000150:complications / Q000235:genetics / Q000821:virology*; D016732:Parvovirus B19, Human / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
D004279:DNA, Viral