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Updated: Feb 17, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response
Jun Chen1,2, Sisi Xia3, Xiangmin Yang4,5
1National Translational Science Center for Molecular Medicine, Xi'an 710032, China. cjun@whu.edu.cn.
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.
Insights
Human Cytomegalovirus (HCMV) evades immune response by targeting CD147 via viral microRNA. This interaction impacts NF-κB and Interferon-beta (IFN-β) signaling, crucial for antiviral defense.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Cellular receptor signaling is vital for initial immune responses to Human Cytomegalovirus (HCMV).
- The role of CD147/EMMPRIN in antiviral responses to HCMV remains uncharacterized.
Purpose of the Study:
- To investigate the involvement of CD147 in the cellular antiviral response to HCMV infection.
- To elucidate the mechanism by which HCMV interacts with CD147 and influences viral propagation.
Main Methods:
- Specific knockdown of CD147 to assess its impact on HCMV-induced signaling pathways.
- Analysis of HCMV-encoded microRNA targeting of CD147 mRNA.
- Measurement of Cyclophilin A (sCyPA) expression and secretion.
- Investigation of the sCyPA-CD147-ERK/NF-κB signaling axis.
Main Results:
- CD147 knockdown significantly reduced HCMV-induced NF-κB and Interferon-beta (IFN-β) activation.
- HCMV-encoded miR-US25-1-5p targets CD147 mRNA's 3' UTR, promoting viral lytic propagation.
- HCMV infection up-regulated the expression and secretion of Cyclophilin A (sCyPA).
- CD147 mediates HCMV-induced antiviral signaling through the sCyPA-CD147-ERK/NF-κB pathway.
Conclusions:
- HCMV utilizes its microRNA to target CD147, thereby evading antiviral innate immunity.
- The sCyPA-CD147-ERK/NF-κB axis is critical for HCMV-triggered antiviral signaling.
- Secreted sCyPA may contribute to HCMV-associated inflammatory disorders.
