Tetraspanin 7 and its closest paralog tetraspanin 6: membrane organizers with key functions in brain development, viral infection, innate immunity, diabetes and cancer

2020 ◽  
Vol 209 (4) ◽  
pp. 427-436 ◽  
Author(s):  
Brieuc P. Perot ◽  
Mickaël M. Ménager
Keyword(s):  
Innate Immunity ◽  
Viral Infection ◽  
Brain Development ◽  
Tetraspanin 7

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.

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 Altered Hippocampal Gene Expression and Morphology in Fetal Piglets following Maternal Respiratory Viral Infection

2018 ◽  
Vol 40 (2) ◽  
pp. 104-119 ◽  
Author(s):  
Adrienne M. Antonson ◽  
Bindu Balakrishnan ◽  
Emily C. Radlowski ◽  
Geraldine Petr ◽  
Rodney W. Johnson
Keyword(s):  
Gene Expression ◽  
Viral Infection ◽  
Brain Development ◽  
Hippocampal Neurons ◽  
Protein A ◽  
Fetal Brain ◽  
Respiratory Syndrome Virus ◽  
Maternal Infection ◽  
Ki 67 ◽  
Fetal Brain Development

Maternal infection during pregnancy increases the risk of neurobehavioral problems in offspring. Evidence from rodent models indicates that the maternal immune response to infection can alter fetal brain development, particularly in the hippocampus. However, information on the effects of maternal viral infection on fetal brain development in gyrencephalic species is limited. Thus, the objective of this study was to assess several effects of maternal viral infection in the last one-third of gestation on hippocampal gene expression and development in fetal piglets. Pregnant gilts were inoculated with porcine reproductive and respiratory syndrome virus (PRRSV) at gestational day (GD) 76 and the fetuses were removed by cesarean section at GD 111 (3 days before anticipated parturition). The gilts infected with PRRSV had elevated plasma interleukin-6 levels and developed transient febrile and anorectic responses lasting approximately 21 days. Despite having a similar overall body weight, fetuses from the PRRSV-infected gilts had a decreased brain weight and altered hippocampal gene expression compared to fetuses from control gilts. Notably, maternal infection caused a reduction in estimated neuronal numbers in the fetal dentate gyrus and subiculum. The number of proliferative Ki-67+ cells was not altered, but the relative integrated density of GFAP+ staining was increased, in addition to an increase in GFAP gene expression, indicating astrocyte-specific gliosis. Maternal viral infection caused an increase in fetal hippocampal gene expression of the inflammatory cytokines TNF-α and IFN-γ and the myelination marker myelin basic protein. MHCII protein, a classic monocyte activation marker, was reduced in microglia, while expression of the MHCII gene was decreased in hippocampal tissue of the fetuses from PRRSV-infected gilts. Together, these data suggest that maternal viral infection at the beginning of the last trimester results in a reduction in fetal hippocampal neurons that is evident 5 weeks after infection, when fetal piglets are near full term. The neuronal reduction was not accompanied by pronounced neuroinflammation at GD 111, indicating that any activation of classic neuroinflammatory pathways by maternal viral infection, if present, is mostly resolved by parturition.

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.

‘Complementing’ viral infection: mechanisms for evading innate immunity

2003 ◽  
Vol 11 (10) ◽  
pp. 449-452 ◽  
Author(s):  
Sun-Hwa Lee ◽  
Jae U Jung ◽  
Robert E Means
Keyword(s):  
Innate Immunity ◽  
Viral Infection ◽  
Infection Mechanisms

Antiviral defense in shrimp: From innate immunity to viral infection

2014 ◽  
Vol 108 ◽  
pp. 129-141 ◽  
Author(s):  
Pei-Hui Wang ◽  
Tianzhi Huang ◽  
Xiaobo Zhang ◽  
Jian-Guo He
Keyword(s):  
Innate Immunity ◽  
Viral Infection ◽  
Antiviral Defense

scholarly journals Roles of Host Immunity in Viral Myocarditis and Dilated Cardiomyopathy

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Lifang Zhao ◽  
Zhaoying Fu
Keyword(s):  
Innate Immunity ◽  
T Cell ◽  
Immune Responses ◽  
Viral Infection ◽  
Dilated Cardiomyopathy ◽  
Viral Myocarditis ◽  
Host Immunity ◽  
Host Immune Responses ◽  
Direct Damage ◽  
Working Together

The pathogenesis of viral myocarditis includes both the direct damage mediated by viral infection and the indirect lesion resulted from host immune responses. Myocarditis can progress into dilated cardiomyopathy that is also associated with immunopathogenesis. T cell-mediated autoimmunity, antibody-mediated autoimmunity (autoantibodies), and innate immunity, working together, contribute to the development of myocarditis and dilated cardiomyopathy.

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.

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