Emerging Roles of Herpesvirus microRNAs During In Vivo Infection and Pathogenesis

Herpesviridae constitutes a large family of double-stranded DNA viruses that are associated with a wide range of diseases, including herpetic lesions, birth defects, and cancer. Herpesviruses establish lifelong latent infections in part because they are exceptionally adept at modulating the virus/host interface. New insights into the numerous roles of microRNAs (miRNAs) in cell biology, along with the recent appreciation that nearly every host transcript is targeted by at least one miRNA, has fundamentally changed our conceptualization of the virus/host relationship. The identification of miRNAs expressed from nearly all human herpesvirus genomes has led to the speculation that these short non-coding transcripts play essential roles in herpesvirus biology. Because the activity of miRNAs depends upon the transcriptome of the cell in which they are expressed, in vivo systems will be essential for defining the true biological relevance of herpesvirus miRNAs. This review will specifically focus on experimental systems which have investigated the functional role of herpesvirus-encoded miRNAs in viral biology and pathogenesis in vivo.