Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Jun, Xia, Sisi, Yang, Xiangmin, Chen, Huizi, Li, Fanni, Liu, Fenyong, Chen, Zhinan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
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
_version_ 1783288695655235584
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
work_keys_str_mv AT chenjun humancytomegalovirusencodedmirus2515pattenuatescd147emmprinmediatedearlyantiviralresponse
AT xiasisi humancytomegalovirusencodedmirus2515pattenuatescd147emmprinmediatedearlyantiviralresponse
AT yangxiangmin humancytomegalovirusencodedmirus2515pattenuatescd147emmprinmediatedearlyantiviralresponse
AT chenhuizi humancytomegalovirusencodedmirus2515pattenuatescd147emmprinmediatedearlyantiviralresponse
AT lifanni humancytomegalovirusencodedmirus2515pattenuatescd147emmprinmediatedearlyantiviralresponse
AT liufenyong humancytomegalovirusencodedmirus2515pattenuatescd147emmprinmediatedearlyantiviralresponse
AT chenzhinan humancytomegalovirusencodedmirus2515pattenuatescd147emmprinmediatedearlyantiviralresponse