Human Cytomegalovirus: The Implications of MicroRNAs in Latency and Therapeutics

Human cytomegalovirus (HCMV) infects the majority of the world’s population. Primary infection is generally asymptomatic in healthy individuals and as with all herpesviruses, a lifelong latency associated with periodical reactivations is established. It is a common congenitally acquired infection and cause of congenital neurological disease. In immunocompromised individuals, such as HIV/AIDS patients and organ transplant recipients, HCMV poses a high risk of severe disease and death. A major cause of opportunistic infections in these individuals, HCMV is able to spread and damage multiple organs by direct cytopathic effects. Due to limitations associated with current therapeutics there is a need for the development of novel therapeutics, particularly for these individuals. MicroRNAs (miRNAs) act as important post-transcriptional regulators for many normal cellular processes in many organisms. In recent years miRNAs have also been identified in a number of double-stranded DNA viruses, including herpesviruses, and have been implicated in the regulation of viral and host genes. As has been observed for a number of other herpesviruses, viral miRNAs are expressed during both lytic infection and latency for HCMV. How HCMV establishes and maintains latency is not fully understood. While studies have clarified some of the roles of miRNAs for lytic HCMV infection, their roles during latent infection are not as defined. This article will provide an overview of what is currently known about HCMV latency, the possible roles of some key host and viral miRNAs in HCMV latency, and a novel therapeutic approach for targeting HCMV latency along with current obstacles to this approach. Understanding how miRNAs contribute to the lifecycle of HCMV and its pathogenesis may change how we approach therapeutics, particularly for organ transplant recipients at risk for severe HCMV-mediated disease.