Transactivation of human parvovirus B19 gene expression in endothelial cells by adenoviral helper functions

Abstract

Human parvovirus B19 (B19V) DNA is highly prevalent in endothelial cells lining up intramyocardial arterioles and postcapillary venules of patients with chronic myocarditis and cardiomyopathies. We addressed the question of a possible stimulation of B19V gene expression in endothelial cells by infection with adenoviruses. Adenovirus infection led to a strong augmentation of B19V structural and nonstructural proteins in individual endothelial cells infected with B19V or transfected with an infectious B19V genome. Transactivation was mostly mediated at the level of transcription and not due to adenovirus-mediated induction of second-strand synthesis from the single-stranded parvoviral genome. The main adenoviral functions required were E1A and E4orf6, which displayed synergistic effects. Furthermore, a limited B19V genome replication could be demonstrated in endothelial cells and adenovirus infection induced the appearance of putative dimeric replication intermediates. Thus the almost complete block in B19V gene expression seen in endothelial cells can be abrogated by infection with other viruses.