Immunomodulatory roles of human herpesvirus‐encoded microRNA in host‐virus interaction

Summary Human herpesviruses (HHV) are large, double stranded, DNA viruses with high seroprevalence across the globe. Clinical manifestation of primary HHV infection resolve shortly, however, this period is prolonged in immunocompromised patients or individuals with suppressed immunity. Examining molecular mechanisms of HHV‐encoded virulence factors can provide finer details of HHV‐host interaction. A unique genetic feature of most members of HHV is that they encode multiple microRNAs (miR). In this review, I will provide mechanistic insights into the immunomodulatory functions of herpesvirus‐encoded viral miR (v‐miR) that favor viral persistence and spread by ingenious immune evasion schemes. Similar to host miR, v‐miR can simultaneously regulate expression of multiple transcripts including host‐ and virus‐derived. V‐miRs, by virtue of their direct interaction with various transcripts, can regulate expression of critical components of host innate and adaptive immune system. V‐miRs are also exported through exosomal route and gain entry into various cells even at distant sites, thereby allowing HHV to manipulate cellular and tissue immunity. Targeting v‐miR may serve as a novel and promising therapeutic candidate to mitigate HHV‐mediated clinical manifestations.