scholarly journals Exosome-mediated apoptosis pathway during WSSV infection in crustacean mud crab

2020 ◽  
Author(s):  
Yi Gong ◽  
Tongtong Kong ◽  
Xin Ren ◽  
Jiao Chen ◽  
Shanmeng Lin ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Viral Infection ◽  
Dna Fragmentation ◽  
Protein Complex ◽  
Cellular Response ◽  
Mud Crab ◽  
Apoptosis Pathway ◽  
Exosomal Mirnas ◽  
Apoptosis Inducing Factor ◽  
Mitochondria Apoptosis Pathway

AbstractMicroRNAs are regulatory molecules that can be packaged into exosomes to modulate recipient’s cellular response, while their role during viral infection is beginning to be appreciated. However, the involvement of exosomal miRNAs during immunoregulation in invertebrates has not been addressed. Here, we found that exosomes released from WSSV-injected mud crabs could suppress viral invasion by inducing apoptosis of hemocytes. Besides, miR-137 and miR-7847 were found to be less packaged in mud crab exosomes during viral infection, with both miR-137 and miR-7847 shown to be negative apoptosis regulators by targeting the apoptosis-inducing factor (AIF). Moreover, our data revealed that AIF did not only translocate to the nucleus to induce DNA fragmentation, but could also competitively bind to HSP70 to disintegrate the HSP70-Bax (Bcl-2-associated X protein) complex, which eventually activated the mitochondria apoptosis pathway via free Bax. Therefore, our findings provides a novel mechanism underlying the crosstalk between exosomal miRNAs and apoptosis pathway in innate immunity in invertebrates.

scholarly journals AMBRA1 promotes apoptosis induced by dsRNA and virus through interacting with and stabilizing MAVS

2021 ◽  
Author(s):  
Yuxia Lin ◽  
Changbai Huang ◽  
Huixin Gao ◽  
Xiaobo Li ◽  
Quanshi Lin ◽  
...  
Keyword(s):  
Viral Infection ◽  
Cellular Response ◽  
Semliki Forest Virus ◽  
Mitochondrial Localization ◽  
Apoptosis Pathway ◽  
Mitochondrial Antiviral Signaling ◽  
Induced Apoptosis ◽  
The Impact ◽  
Mitochondrial Antiviral Signaling Protein

Apoptosis is an important cellular response to viral infection. In current study, we identified activating molecule in Beclin1-regulated autophagy protein 1 (AMBRA1) as a positive regulator of apoptosis triggered by dsRNA. Depletion of AMBRA1 by gene editing significantly reduced dsRNA-induced apoptosis, which was largely restored by trans-complementation of AMBRA1. Mechanistically, AMBRA1 interacts with mitochondrial antiviral-signaling protein (MAVS), a key mitochondrial adaptor in the apoptosis pathway induced by dsRNA and viral infection. Further Co-IP analysis demonstrated that the mitochondrial localization of MAVS was essential for their interaction. The impact of AMBRA1 on dsRNA-induced apoptosis relied on the presence of MAVS and caspase-8. AMBRA1 was involved in the stabilization of MAVS through preventing its proteasomal degradation induced by dsRNA. Consistently, AMBRA1 upregulated the apoptosis induced by Semliki Forest virus infection. Taken together, our work illustrated a role of AMBRA1 in the virus-induced apoptosis through interacting with and stabilizing MAVS.

scholarly journals Role of Alternative Splicing in Regulating Host Response to Viral Infection

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1720
Author(s):  
Kuo-Chieh Liao ◽  
Mariano A. Garcia-Blanco
Keyword(s):  
Innate Immunity ◽  
Alternative Splicing ◽  
Immune Responses ◽  
Viral Infection ◽  
Rna Splicing ◽  
Type I ◽  
Host Immune Responses ◽  
Transcriptional Regulatory Mechanisms ◽  
Host Virus Interactions

The importance of transcriptional regulation of host genes in innate immunity against viral infection has been widely recognized. More recently, post-transcriptional regulatory mechanisms have gained appreciation as an additional and important layer of regulation to fine-tune host immune responses. Here, we review the functional significance of alternative splicing in innate immune responses to viral infection. We describe how several central components of the Type I and III interferon pathways encode spliced isoforms to regulate IFN activation and function. Additionally, the functional roles of splicing factors and modulators in antiviral immunity are discussed. Lastly, we discuss how cell death pathways are regulated by alternative splicing as well as the potential role of this regulation on host immunity and viral infection. Altogether, these studies highlight the importance of RNA splicing in regulating host–virus interactions and suggest a role in downregulating antiviral innate immunity; this may be critical to prevent pathological inflammation.

A new crustin homologue (SpCrus6) involved in the antimicrobial and antiviral innate immunity in mud crab, Scylla paramamosain

2019 ◽  
Vol 84 ◽  
pp. 733-743 ◽  
Author(s):  
Zhi-qiang Du ◽  
Yue Wang ◽  
Hong-yu Ma ◽  
Xiu-li Shen ◽  
Kai Wang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Scylla Paramamosain ◽  
Mud Crab ◽  
Antiviral Innate Immunity

scholarly journals Sodium citrate inhibits proliferation and induces apoptosis of hepatocellular carcinoma cells

2020 ◽  
Vol 7 (3) ◽  
pp. 3659-3666
Author(s):  
Phuc Hong Vo ◽  
Sinh Truong Nguyen ◽  
Nghia Minh Do ◽  
Kiet Dinh Truong ◽  
Phuc Van Pham
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Cells ◽  
Dna Fragmentation ◽  
Hepg2 Cells ◽  
Annexin V ◽  
Carcinoma Cells ◽  
Human Gastric Cancer ◽  
Apoptosis Pathway ◽  
Hepatocellular Carcinoma Cells ◽  
Activation Assay

Introduction: Cancer cells rely on glycolysis to generate energy and synthesize biomass for cell growth and proliferation (the Warburg effect). Recent studies have shown that citrate has an inhibitory effect on several cancer cells, such as human gastric cancer and ovarian cancer, by inhibiting glycolysis. In this study, we investigated the effects of citrate on the proliferation and apoptosis induction of hepatocellular carcinoma cells. Methods: HepG2 hepatocellular carcinoma cell line was used in this study. The cell proliferation was evaluated by Alamar blue assay. The apoptotic status of the HepG2 cells was recorded by Annexin V/7-AAD assay and caspase 3/7 activation assay. DNA fragmentation was evaluated by nucleus staining assay with Hoechst 33342. Results: The results showed that citrate is able to inhibit the proliferation of HepG2 cells and induce apoptosis in these cells. The initiation time of apoptosis is 4 hours after treatment with 10 mM citrate. Morphology characteristics of DNA fragmentation and broken membranes were also recorded in the apoptotic cells. Conclusion: In conclusion, our study demonstrates that citrate causes HepG2 cell death by the apoptosis pathway.

scholarly journals Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Negatively Regulates Innate Immunity Against RNA Virus by Targeting RIG-I in Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Ziqi Zou ◽  
Mengyao Li ◽  
Yunlian Zhou ◽  
Jiaying Li ◽  
Ting Pan ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Retinoic Acid ◽  
Viral Infection ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Rna Virus ◽  
Type I ◽  
Factor Α ◽  
Necrosis Factor ◽  
Inducible Gene

A systematic and flexible immunoregulatory network is required to ensure the proper outcome of antiviral immune signaling and maintain homeostasis during viral infection. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2), a novel immunoregulatory protein, has been extensively studied in inflammatory response, apoptosis, and cancer. However, the function of TIPE2 in antiviral innate immunity is poorly clarified. In this study, we reported that the expression of TIPE2 declined at the early period and then climbed up in macrophages under RNA virus stimulation. Knockout of TIPE2 in the macrophages enhanced the antiviral capacity and facilitated type I interferon (IFN) signaling after RNA viral infection both in vitro and in vivo. Consistently, overexpression of TIPE2 inhibited the production of type I IFNs and pro-inflammatory cytokines, and thus promoted the viral infection. Moreover, TIPE2 restrained the activation of TBK1 and IRF3 in the retinoic acid inducible gene-I (RIG-I)-like receptors (RLR) signaling pathway by directly interacting with retinoic acid inducible gene-I (RIG-I). Taken together, our results suggested that TIPE2 suppresses the type I IFN response induced by RNA virus by targeting RIG-I and blocking the activation of downstream signaling. These findings will provide new insights to reveal the immunological function of TIPE2 and may help to develop new strategies for the clinical treatment of RNA viral infections.

scholarly journals Unmasking cellular response of a bloom-forming alga to viral infection by resolving expression profiles at a single-cell level

2019 ◽  
Vol 15 (4) ◽  
pp. e1007708 ◽  
Author(s):  
Shilo Rosenwasser ◽  
Uri Sheyn ◽  
Miguel J. Frada ◽  
David Pilzer ◽  
Ron Rotkopf ◽  
...  
Keyword(s):  
Viral Infection ◽  
Single Cell ◽  
Cellular Response ◽  
Expression Profiles ◽  
Single Cell Level ◽  
Cell Level

scholarly journals ISG12a Restricts Hepatitis C Virus Infection through the Ubiquitination-Dependent Degradation Pathway

2016 ◽  
Vol 90 (15) ◽  
pp. 6832-6845 ◽  
Author(s):  
Binbin Xue ◽  
Darong Yang ◽  
Jingjing Wang ◽  
Yan Xu ◽  
Xiaohong Wang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Infection ◽  
Viral Protein ◽  
E3 Ligase ◽  
Antiviral Effect ◽  
Degradation Pathway ◽  
Viral Spread ◽  
Ubiquitin E3 Ligase

ABSTRACTInterferons (IFNs) restrict various kinds of viral infection via induction of hundreds of IFN-stimulated genes (ISGs), while the functions of the majority of ISGs are broadly unclear. Here, we show that a high-IFN-inducible gene, ISG12a (also known as IFI27), exhibits a nonapoptotic antiviral effect on hepatitis C virus (HCV) infection. Viral NS5A protein is targeted specifically by ISG12a, which mediates NS5A degradation via a ubiquitination-dependent proteasomal pathway. K374R mutation in NS5A domain III abrogates ISG12a-induced ubiquitination and degradation of NS5A. S-phase kinase-associated protein 2 (SKP2) is identified as an ubiquitin E3 ligase for NS5A. ISG12a functions as a crucial adaptor that promotes SKP2 to interact with and degrade viral protein. Moreover, the antiviral effect of ISG12a is dependent on the E3 ligase activity of SKP2. These findings uncover an intriguing mechanism by which ISG12a restricts viral infection and provide clues for understanding the actions of innate immunity.IMPORTANCEUpon virus invasion, IFNs induce numerous ISGs to control viral spread, while the functions of the majority of ISGs are broadly unclear. The present study shows a novel antiviral mechanism of ISGs and elucidated that ISG12a recruits an E3 ligase, SKP2, for ubiquitination and degradation of viral protein and restricts viral infection. These findings provide important insights into exploring the working principles of innate immunity.

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