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Novel Fatty Acid in Cordyceps Suppresses Influenza A (H1N1) Virus-Induced Proinflammatory Response Through Regulating Innate Signaling Pathways.

ABSTRACT: Influenza virus (IV) infections usually cause acute lung injury characterized by exaggerated proinflammatory responses. The paucity of therapeutic strategies that target host immune response to attenuate lung injury poses a substantial challenge in management of IV infections. In this study, we chemically synthesized a novel fatty acid (2Z,4E)-deca-2,4-dienoic acid (DDEA) identified from Chinese Cordyceps by using UHPLC-Q-TOF-MS techniques. The DDEA did not inhibit H1N1 virus replication but attenuated proinflammatory responses by reducing mRNA and protein levels of TNF-?, IFN-?, IFN-?, IL-6, CXCL-8/IL-8, CCL-2/MCP-1, CXCL-10/IP-10, CCL-3/MIP-1?, and CCL-4/MIP-1? in A549 cells and U937-derived macrophages. The anti-inflammatory effect occurred through downregulations of TLR-3-, RIG-I-, and type I IFN-activated innate immune signaling pathways. Altogether, our results indicate that DDEA may potentially be used as an anti-inflammatory therapy for the treatment of IV infections.

SUBMITTER: Li RF

PROVIDER: S-EPMC7818636 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Novel Fatty Acid in Cordyceps Suppresses Influenza A (H1N1) Virus-Induced Proinflammatory Response Through Regulating Innate Signaling Pathways.

Li Run-Feng RF Zhou Xiao-Bo XB Zhou Hong-Xia HX Yang Zi-Feng ZF Jiang Hai-Ming HM Wu Xiao X Li Wen-Jia WJ Qiu Jian-Jian JJ Mi Jia-Ning JN Chen Ming M Zhong Nan-Shan NS Zhu Guo-Yuan GY Jiang Zhi-Hong ZH

ACS omega 20210107 2

Influenza virus (IV) infections usually cause acute lung injury characterized by exaggerated proinflammatory responses. The paucity of therapeutic strategies that target host immune response to attenuate lung injury poses a substantial challenge in management of IV infections. In this study, we chemically synthesized a novel fatty acid (2Z,4E)-deca-2,4-dienoic acid (DDEA) identified from Chinese Cordyceps by using UHPLC-Q-TOF-MS techniques. The DDEA did not inhibit H1N1 viru ...[more]

PMID: 33490810

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Project description:Influenza A virus (IAV) is a highly contagious pathogen, causing acute respiratory illnesses in human beings and animals and frequently giving rise to epidemic outbreaks. Evasion by IAV of host immunity facilitates viral replication and spread, which can be initiated through various mechanisms, including epidermal growth factor receptor (EGFR) activation. However, how EGFR mediates the suppression of antiviral systems remains unclear. Here, we examined host innate immune responses and their relevant signaling to EGFR upon IAV infection. IAV was found to induce the phosphorylation of EGFR and extracellular signal-regulated kinase (ERK) at an early stage of infection. Inhibition of EGFR or ERK suppressed the viral replication but increased the expression of type I and type III interferons (IFNs) and interferon-stimulated genes (ISGs), supporting the idea that IAV escapes from antiviral innate immunity by activating EGFR/ERK signaling. Meanwhile, IAV infection also induced the activation of Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2). Pharmacological inhibition or small interfering RNA (siRNA)-based silencing of SHP2 enhanced the IFN-dependent antiviral activity and reduced virion production. Furthermore, knockdown of SHP2 attenuated the EGFR-mediated ERK phosphorylation triggered by viral infection or EGF stimulation. Conversely, ectopic expression of constitutively active SHP2 noticeably promoted ERK activation and viral replication, concomitant with diminished immune function. Altogether, the results indicate that SHP2 is crucial for IAV-induced activation of the EGFR/ERK pathway to suppress host antiviral responses.IMPORTANCE Viral immune evasion is the most important strategy whereby viruses evolve for their survival. This work shows that influenza A virus (IAV) suppressed the antiviral innate immunity through downregulation of IFNs and ISGs by activating EGFR/ERK signaling. Meanwhile, IAV also induced the activation of protein tyrosine phosphatase SHP2, which was found to be responsible for modulating the EGFR-mediated ERK activity and subsequent antiviral effectiveness both in vitro and in vivo The results suggest that SHP2 is a key signal transducer between EGFR and ERK and plays a crucial role in suppressing host innate immunity during IAV infection. The finding enhances our understanding of influenza immune evasion and provides a new therapeutic approach to viral infection.

Dataset Information

Novel Fatty Acid in Cordyceps Suppresses Influenza A (H1N1) Virus-Induced Proinflammatory Response Through Regulating Innate Signaling Pathways.

Publications

Novel Fatty Acid in <i>Cordyceps</i> Suppresses Influenza A (H1N1) Virus-Induced Proinflammatory Response Through Regulating Innate Signaling Pathways.

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