Viral gene products actively promote latent infection by epigenetic silencing mechanisms

•Viruses such as the herpesviruses and HIV establish latent infections.•DNA viruses undergo epigenetic silencing to establish a latent infection.•Viruses encode their own gene products that promote epigenetic silencing of their genome.•Viral proteins promoting latent genome silencing are potential targets for therapeutic agents.

Many viruses undergo an acute infection in the host organism and then are cleared by the ensuing host immune response, but other viruses establish a persistent infection involving a latent infection or a chronic infection. Latent infection by the herpesviruses or human immunodeficiency virus involves epigenetic silencing of the DNA genome or proviral genome, respectively. Latent infection was previously thought to be a default pathway resulting from infection of a nonpermissive cell, but recent studies have shown that viral gene products can promote epigenetic silencing and latent infection. This review will summarize the viral gene products that have been shown to promote epigenetic silencing of the genomes and their potential for therapeutics to target these viral gene products and disrupt or lock in latent infection.