Molecular Regulatory Networks Governing Replication, Gene Expression, and Host–Virus Interactions of Human Double-Stranded DNA Viruses: A Comprehensive Review

Abstract

The group of double-stranded DNA (dsDNA) viruses is a heterogeneous group of pathogens characterized by wide variability in genome sizes, structure, modes of replication, gene expression, and interaction with host cells. Success of dsDNA viruses is linked to precise molecular regulation of viral genome replication, transcription, translation, assembly, immune system evasion, as well as persistent or latent infection observed for some virus families. This review focuses on molecular mechanisms underlying the replication and gene expression of important dsDNA viruses, with special attention to the networks regulating virus and host functions throughout the infection process. Time-dependent regulation of gene expression, including immediate-early, early, and late transcription, as well as participation of viral and host transcription factors, promoter and enhancer sequences, chromatin remodeling, and epigenetic changes are considered. Replication strategies of nuclear and cytoplasmic replicating dsDNA viruses, including bidirectional replication, formation of concatemers, strand displacement, and replication in viral replication compartments are analyzed. Special In addition, the review highlights the key ways by which dsDNA viruses control host-cell signaling, innate and adaptive immunity, apoptosis, cell cycle, antigen presentation, and gene expression within the cell. Specifically, special focus is placed on viral latency, persistence, and reactivation, which are particularly common in case of herpesviruses and other viruses that can cause long-lasting infections. Finally, the medical relevance of the most important dsDNA viruses in humans and corresponding treatment options, vaccinations, difficulties with therapeutic approaches, and mechanisms of antiviral resistance are described. The comprehensive knowledge about viral regulatory pathways and interactions between viruses and host cells will be instrumental for the discovery of new antiviral targets.