Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response
Jun Chen 1,2, Sisi Xia 3, Xiangmin Yang 1,2, Huizi Chen 4, Fanni Li 1,2
, Fenyong Liu 5 and Zhinan Chen 1,2,*
, Fenyong Liu 5 and Zhinan Chen 1,2,*
1
National Translational Science Center for Molecular Medicine, Xi’an 710032, China
2
Cell Engineering Research Center & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an 710032, China
3
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
4
Department of Immunology, Zunyi Medical College, Guizhou 563000, China
5
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA 94720, USA
*
Author to whom correspondence should be addressed.
Viruses 2017, 9(12), 365; https://doi.org/10.3390/v9120365
Received: 26 October 2017 / Revised: 23 November 2017 / Accepted: 28 November 2017 / Published: 1 December 2017
Abstract
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. View Full-TextKeywords:
human cytomegalovirus (HCMV); CD147/EMMPRIN; miR-US25-1-5p; cyclophilin A (CyPA); ERK/NF-κB signaling pathway; HCMV inflammatory disorders
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Chen, J.; Xia, S.; Yang, X.; Chen, H.; Li, F.; Liu, F.; Chen, Z. Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response. Viruses 2017, 9, 365.
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