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 (M?) are important component of immune surveillance in oral mucosa. Depending on the activation status, M? are categorized as classical proinflammatory (M1) and alternative antiinflammatory (M2).
We aim to characterize the role of our previously identified candidate vmiRs in regulating M? plasticity through modulation of host miRNAs. The impact of vmiR mediated differential expression of cellular and exosomal miRNA profiles of M1 and M2 M? will be assessed. VmiR mediated functional modulation of M? 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 M? 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.

Public Health Relevance

The oral cavity is a niche to diverse microbes including viruses. Herpesviruses are predominant as latent infections among the human population and can reactivate under certain conditions. Small regulatory RNAs encoded by viruses (vmiRs) are important in viral persistence and their levels change during inflammation. Macrophages are key immune cells that reside in oral mucosa. Two different categories of macrophages are known that elicit specific immune responses. The focus of our study is to investigate how vmiRs functionally modulate each type of macrophage. Further, the impact of exosomes (secreted nanovesicles) from vmiR expressing macrophages will be assessed on the key functions of neighboring oral keratinocytes. The knowledge to be gained from this study will be utilized to develop therapeutic targets which will be of value to medicine and dentistry.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1)
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Chander, Preethi
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University of Illinois at Chicago
Schools of Dentistry/Oral Hygn
United States
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Naqvi, Afsar R; Brambila, Maria F; Martínez, Gloria et al. (2018) Dysregulation of human miRNAs and increased prevalence of HHV miRNAs in obese periodontitis subjects. J Clin Periodontol :
Naqvi, Afsar R; Shango, Jennifer; Seal, Alexandra et al. (2018) Viral miRNAs Alter Host Cell miRNA Profiles and Modulate Innate Immune Responses. Front Immunol 9:433
Naqvi, Afsar R; Seal, Alexandra; Shango, Jennifer et al. (2018) Herpesvirus-encoded microRNAs detected in human gingiva alter host cell transcriptome and regulate viral infection. Biochim Biophys Acta Gene Regul Mech 1861:497-508
Naqvi, Afsar R; Seal, Alexandra; Shango, Jennifer et al. (2018) In silico prediction of cellular gene targets of herpesvirus encoded microRNAs. Data Brief 19:249-255
Naqvi, Afsar R; Shango, Jennifer; Seal, Alexandra et al. (2018) Herpesviruses and MicroRNAs: New Pathogenesis Factors in Oral Infection and Disease? Front Immunol 9:2099
Self-Fordham, Jezrom Bokcaerin; Naqvi, Afsar Raza; Uttamani, Juhi Raju et al. (2017) MicroRNA: Dynamic Regulators of Macrophage Polarization and Plasticity. Front Immunol 8:1062