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Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response
Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV) infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) in the antiviral response to HC...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744140/ https://www.ncbi.nlm.nih.gov/pubmed/29194430 http://dx.doi.org/10.3390/v9120365 |
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author | Chen, Jun Xia, Sisi Yang, Xiangmin Chen, Huizi Li, Fanni Liu, Fenyong Chen, Zhinan |
author_facet | Chen, Jun Xia, Sisi Yang, Xiangmin Chen, Huizi Li, Fanni Liu, Fenyong Chen, Zhinan |
author_sort | Chen, Jun |
collection | PubMed |
description | Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV) infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) in the antiviral response to HCMV infection is still unknown. Here, we demonstrated the specific knockdown of CD147 significantly decreased HCMV-induced activation of NF-κB and Interferon-beta (IFN-β), which contribute to the cellular antiviral responses. Next, we confirmed that HCMV-encoded miR-US25-1-5p could target the 3′ UTR (Untranslated Region) of CD147 mRNA, and thus facilitate HCMV lytic propagation at a low multiplicity of infection (MOI). The expression and secretion of Cyclophilin A (sCyPA), as a ligand for CD147 and a proinflammatory cytokine, were up-regulated in response to HCMV stimuli. Finally, we confirmed that CD147 mediated HCMV-triggered antiviral signaling via the sCyPA-CD147-ERK (extracellular regulated protein kinases)/NF-κB axis signaling pathway. These findings reveal an important HCMV mechanism for evading antiviral innate immunity through its encoded microRNA by targeting transmembrane glycoprotein CD147, and a potential cause of HCMV inflammatory disorders due to the secretion of proinflammatory cytokine CyPA. |
format | Online Article Text |
id | pubmed-5744140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-57441402017-12-31 Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response Chen, Jun Xia, Sisi Yang, Xiangmin Chen, Huizi Li, Fanni Liu, Fenyong Chen, Zhinan Viruses Article Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV) infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) in the antiviral response to HCMV infection is still unknown. Here, we demonstrated the specific knockdown of CD147 significantly decreased HCMV-induced activation of NF-κB and Interferon-beta (IFN-β), which contribute to the cellular antiviral responses. Next, we confirmed that HCMV-encoded miR-US25-1-5p could target the 3′ UTR (Untranslated Region) of CD147 mRNA, and thus facilitate HCMV lytic propagation at a low multiplicity of infection (MOI). The expression and secretion of Cyclophilin A (sCyPA), as a ligand for CD147 and a proinflammatory cytokine, were up-regulated in response to HCMV stimuli. Finally, we confirmed that CD147 mediated HCMV-triggered antiviral signaling via the sCyPA-CD147-ERK (extracellular regulated protein kinases)/NF-κB axis signaling pathway. These findings reveal an important HCMV mechanism for evading antiviral innate immunity through its encoded microRNA by targeting transmembrane glycoprotein CD147, and a potential cause of HCMV inflammatory disorders due to the secretion of proinflammatory cytokine CyPA. MDPI 2017-12-01 /pmc/articles/PMC5744140/ /pubmed/29194430 http://dx.doi.org/10.3390/v9120365 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Jun Xia, Sisi Yang, Xiangmin Chen, Huizi Li, Fanni Liu, Fenyong Chen, Zhinan Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response |
title | Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response |
title_full | Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response |
title_fullStr | Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response |
title_full_unstemmed | Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response |
title_short | Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response |
title_sort | human cytomegalovirus encoded mir-us25-1-5p attenuates cd147/emmprin-mediated early antiviral response |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744140/ https://www.ncbi.nlm.nih.gov/pubmed/29194430 http://dx.doi.org/10.3390/v9120365 |
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