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Viral miRNAs Alter Host Cell miRNA Profiles and Modulate Innate Immune Responses
Prevalence of the members of herpesvirus family in oral inflammatory diseases is increasingly acknowledged suggesting their likely role as an etiological factor. However, the underlying mechanisms remain obscure. In our recent miRNA profiling of healthy and diseased human tooth pulps, elevated expre...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845630/ https://www.ncbi.nlm.nih.gov/pubmed/29559974 http://dx.doi.org/10.3389/fimmu.2018.00433 |
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author | Naqvi, Afsar R. Shango, Jennifer Seal, Alexandra Shukla, Deepak Nares, Salvador |
author_facet | Naqvi, Afsar R. Shango, Jennifer Seal, Alexandra Shukla, Deepak Nares, Salvador |
author_sort | Naqvi, Afsar R. |
collection | PubMed |
description | Prevalence of the members of herpesvirus family in oral inflammatory diseases is increasingly acknowledged suggesting their likely role as an etiological factor. However, the underlying mechanisms remain obscure. In our recent miRNA profiling of healthy and diseased human tooth pulps, elevated expression of human herpesvirus encoded viral microRNAs (v-miRs) were identified. Based on the fold induction and significance values, we selected three v-miRs namely miR-K12-3-3p [Kaposi sarcoma-associated virus (KSHV)], miR-H1 [herpes simplex virus 1 (HSV1)], and miR-UL-70-3p [human cytomegalovirus (HCMV)] to further examine their impact on host cellular functions. We examined their impact on cellular miRNA profiles of primary human oral keratinocytes (HOK). Our results show differential expression of several host miRNAs in v-miR-transfected HOK. High levels of v-miRs were detected in exosomes derived from v-miR transfected HOK as well as the KSHV-infected cell lines. We show that HOK-derived exosomes release their contents into macrophages (Mφ) and alter expression of endogenous miRNAs. Concurrent expression analysis of precursor (pre)-miRNA and mature miRNA suggest transcriptional or posttranscriptional impact of v-miRs on the cellular miRNAs. Employing bioinformatics, we predicted several pathways targeted by deregulated cellular miRNAs that include cytoskeletal organization, endocytosis, and cellular signaling. We validated three novel targets of miR-K12-3-3p and miR-H1 that are involved in endocytic and intracellular trafficking pathways. To evaluate the functional consequence of this regulation, we performed phagocytic uptake of labeled bacteria and noticed significant attenuation in miR-H1 and miR-K12-3-3p but not miR-UL70-3p transfected primary human Mφ. Multiple cytokine analysis of E. coli challenged Mφ revealed marked reduction of secreted cytokine levels with important roles in innate and adaptive immune responses suggesting a role of v-miRs in immune subversion. Our findings reveal that oral disease associated v-miRs can dysregulate functions of key host cells that shape oral mucosal immunity thus exacerbating disease severity and progression. |
format | Online Article Text |
id | pubmed-5845630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58456302018-03-20 Viral miRNAs Alter Host Cell miRNA Profiles and Modulate Innate Immune Responses Naqvi, Afsar R. Shango, Jennifer Seal, Alexandra Shukla, Deepak Nares, Salvador Front Immunol Immunology Prevalence of the members of herpesvirus family in oral inflammatory diseases is increasingly acknowledged suggesting their likely role as an etiological factor. However, the underlying mechanisms remain obscure. In our recent miRNA profiling of healthy and diseased human tooth pulps, elevated expression of human herpesvirus encoded viral microRNAs (v-miRs) were identified. Based on the fold induction and significance values, we selected three v-miRs namely miR-K12-3-3p [Kaposi sarcoma-associated virus (KSHV)], miR-H1 [herpes simplex virus 1 (HSV1)], and miR-UL-70-3p [human cytomegalovirus (HCMV)] to further examine their impact on host cellular functions. We examined their impact on cellular miRNA profiles of primary human oral keratinocytes (HOK). Our results show differential expression of several host miRNAs in v-miR-transfected HOK. High levels of v-miRs were detected in exosomes derived from v-miR transfected HOK as well as the KSHV-infected cell lines. We show that HOK-derived exosomes release their contents into macrophages (Mφ) and alter expression of endogenous miRNAs. Concurrent expression analysis of precursor (pre)-miRNA and mature miRNA suggest transcriptional or posttranscriptional impact of v-miRs on the cellular miRNAs. Employing bioinformatics, we predicted several pathways targeted by deregulated cellular miRNAs that include cytoskeletal organization, endocytosis, and cellular signaling. We validated three novel targets of miR-K12-3-3p and miR-H1 that are involved in endocytic and intracellular trafficking pathways. To evaluate the functional consequence of this regulation, we performed phagocytic uptake of labeled bacteria and noticed significant attenuation in miR-H1 and miR-K12-3-3p but not miR-UL70-3p transfected primary human Mφ. Multiple cytokine analysis of E. coli challenged Mφ revealed marked reduction of secreted cytokine levels with important roles in innate and adaptive immune responses suggesting a role of v-miRs in immune subversion. Our findings reveal that oral disease associated v-miRs can dysregulate functions of key host cells that shape oral mucosal immunity thus exacerbating disease severity and progression. Frontiers Media S.A. 2018-03-06 /pmc/articles/PMC5845630/ /pubmed/29559974 http://dx.doi.org/10.3389/fimmu.2018.00433 Text en Copyright © 2018 Naqvi, Shango, Seal, Shukla and Nares. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Naqvi, Afsar R. Shango, Jennifer Seal, Alexandra Shukla, Deepak Nares, Salvador Viral miRNAs Alter Host Cell miRNA Profiles and Modulate Innate Immune Responses |
title | Viral miRNAs Alter Host Cell miRNA Profiles and Modulate Innate Immune Responses |
title_full | Viral miRNAs Alter Host Cell miRNA Profiles and Modulate Innate Immune Responses |
title_fullStr | Viral miRNAs Alter Host Cell miRNA Profiles and Modulate Innate Immune Responses |
title_full_unstemmed | Viral miRNAs Alter Host Cell miRNA Profiles and Modulate Innate Immune Responses |
title_short | Viral miRNAs Alter Host Cell miRNA Profiles and Modulate Innate Immune Responses |
title_sort | viral mirnas alter host cell mirna profiles and modulate innate immune responses |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845630/ https://www.ncbi.nlm.nih.gov/pubmed/29559974 http://dx.doi.org/10.3389/fimmu.2018.00433 |
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