Human herpesvirus-encoded MicroRNA in host-pathogen interaction.

ABSTRACT

Human herpesviruses (HHV) are ubiquitous, linear dsDNA viruses that establish lifelong latency, disrupted by sporadic reactivation. HHV have evolved diverse ingenious mechanisms to evade robust host defenses. Incorporation of unique stem loop sequences that generate viral microRNAs (v-miRs) exemplifies one such evolutionary adaptation in HHV. These noncoding RNAs can control cellular and viral transcriptomes highlighting their ability in shaping host-HHV interactions. We summarize recent developments in functional characterization of HHV-encoded miRNAs in shaping the outcome of host-pathogen interaction. Non-immunogenic dissemination of v-miRs through exosomes confer added advantage to HHV in incessant modulation of host microenvironment. This review delineates the mechanistic role of v-miRs in facilitating viral persistence and tropism by targeting genes associated with cellular (apoptosis, angiogenesis, cell migration, etc.) and viral life cycle (latency, lytic and reactivation). Burgeoning evidences indicate plausible association of v-miRs in various immune-mediated diseases (nasopharyngeal carcinoma, neurological disorders, periodontal diseases, etc.) and herpesvirus-related malignancies indicating their broad-spectrum impact on host cellular pathways. We propose to exploit tisssue and systemic levels of v-miRs as diagnostic and prognostic markers for cancers and immune-mediated diseases. Therapeutic targeting of v-miRs will advance the promising outcomes of preclinical discoveries to bedside application.