Targeting histone epigenetics to control viral infections

During the past decades, many studies have significantly broadened our understanding of complex virus-host interactions to control chromatin structure and dynamics.1, 2 However, the role and impact of such modifications during viral infections is not fully revealed. Indeed, this type of regulation is bidirectional between the virus and the host. While viral replication and gene expression are significantly impacted by histone modifications on the viral chromatin,(3) studies have shown that some viral pathogens dynamically manipulate cellular epigenetic factors to enhance their own survival and pathogenesis, as well as escape the immune system defense lines.(4) In this dynamic, histone posttranslational modifications (PTMs) appear to play fundamental roles in the regulation of chromatin structure and recruitment of other factors.(5) Genuinely, those PTMs play a vital role in lytic infection, latency reinforcement, or, conversely, viral reactivation.(6) In this chapter, we will examine and review the involvement of histone modifications as well as their potential manipulation to control infections during various viral life cycle stages, highlighting their prospective implications in the clinical management of human immunodeficiency virus (HIV), herpes simplex virus (HSV), human cytomegalovirus (HCMV), hepatitis B and C viruses (HBV and HCV, respectively), Epstein–Barr virus (EBV), and other viral diseases. Targeting histone modifications is critical in setting the treatment of chronic viral infections with both lytic and latent stages (HIV, HCMV, HSV, RSV), virus-induced cancers (HBV, HCV, EBV, KSHV, HPV), and epidemic/emerging viruses (e.g. influenza virus, arboviruses).