Characterizing the role of viral microRNAs in regulating macrophage plasticity

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Characterizing the role of viral microRNAs in regulating macrophage plasticity Afsar Raza Naqvi, Ph.D. Emerging evidences show implication of human herpesviruses (HHV) infection in oral inflammatory diseases. These viruses establish lifelong infection which requires immune evasion. HHV, like eukaryotes, encode microRNAs (miRNA) which are non-protein coding regulatory RNAs. MiRNAs binds to and silence target gene expression thereby controlling various biological processes including cell differentiation, apoptosis, immune responses, etc. Viral miRNAs (vmiRs) play critical role in pathogenesis as they can regulate expression of both virus and host derived transcripts. In our preliminary studies, we identified induced levels of several vmiRs in biopsies from patients with inflamed pulps or diseased gingiva. Macrophages (Mφ) are important component of immune surveillance in oral mucosa. Depending on the activation status, Mφ are categorized as classical proinflammatory (M1) and alternative antiinflammatory (M2). We aim to characterize the role of our previously identified candidate vmiRs in regulating Mφ plasticity through modulation of host miRNAs. The impact of vmiR mediated differential expression of cellular and exosomal miRNA profiles of M1 and M2 Mφ will be assessed. VmiR mediated functional modulation of Mφ plasticity will be assessed by examining phenotype associated markers. This aspect has not been investigated earlier and will likely provide novel insights on the role of vmiR in the pathogenesis of oral diseases. Dynamic interaction of myeloid cells with surrounding oral keratinocytes is required to amplify innate immune responses for a favorable outcome. The effect of exosomes derived from vmiR expressing M1 and M2 Mφ will be examined on key biological functions of primary human oral keratinocytes including innate immune responses, cell proliferation and migration. The data generated will provide significant information to address existing knowledge gaps. Importantly, as vmiRs are not endogenous RNAs, they have the potential to be deployed as potential therapeutic targets.