How Influenza A Virus NS1 Deals with the Ubiquitin System to Evade Innate Immunity

Lamotte, Laurie-Anne; Tafforeau, Lionel

doi:10.3390/v13112309

Cited by 17 publications

(16 citation statements)

References 347 publications

(435 reference statements)

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“…Alternatively, IFITM1, an interferon-induced transmembrane protein, is signi cantly upregulated by IFN-β stimulation. IFITM1 was proven to be more effective in resisting the in uenza virus infection by blocking the fusion of the viral particle with the cellular host membrane during the uncoating step [34,35]. TRIM22 expression is also upregulated by IFN-β in response to IAV infection and has been reported to be a marker of activation of the type I IFN system in A549 cells.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Interferon Stimulated Genes Enhance Viral Replication of Seasonal Influenza A Virus through the JAK/STAT pathway

Kakee

Kageyama

et al. 2022

Preprint

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Background In a previous study, we described the diverse growth capabilities of circulating seasonal influenza A virus (IAV) with low to high viral copies in vitro. In this study, we analyzed the cause of differences in growth capability by evaluating Interferon-β and antiviral interferon-stimulated genes (ISGs) expression. Methods A549 cells (3.0x105 cells) were inoculated with circulating seasonal IAV strains for 6 and 24 h. In cells inoculated for 6 h, IAV production was assessed by IAV-RNA copies in culture supernatant and cell pellets for gene expression evaluation. At 24 hours post-infection, cells were collected for IFN-β and ISG-15 protein expression. JAK/STAT pathway inhibitor, pyridone 6 (P6) was used to evaluate the influence of ISGs on the growth capability of seasonal IAV. Results A549 cells inoculated with seasonal IAV strains with high growth capability expressed less IFN-β and ISGs, whereas low growth capability strains expressed more IFN-β and ISGs. The use of a P6, a JAK/STAT inhibitor, suppressed the expression of ISGs and enhanced the viral copies of seasonal IAV strains with low growth capability. This result suggests that growth capability is regulated by ISG-mediated IFN-β production. Conclusion In this study, we provide a new insight into the mechanism of circulating seasonal IAV replication. Our study showed that the difference in the growth capability of circulating seasonal IAV strains is due to the regulation of antiviral ISGs. Inhibition of the JAK/STAT pathway permits seasonal IAV strains with low growth capability to enhance their viral copies by suppressing antiviral ISGs. Our results may contribute in developing new effective therapeutic strategies and reduce the risk of developing severe influenza disease.

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Section: Discussionmentioning

confidence: 99%

Suppression of Interferon Stimulated Genes Enhance Viral Replication of Seasonal Influenza A Virus through the JAK/STAT pathway

Kakee

Kageyama

et al. 2022

Preprint

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“…Interestingly, we detected for both, GAS mono-infection and superinfection an upregulation of Il1b, which suggests that the incapacity of co-infected macrophages to process and secrete IL-1β is due to a failure in the GAS-inducible activation of the NLRP3 inflammasome [86][87][88][89]. In fact, it was shown that different variants of IAV, including a 2009 pandemic strain, were capable of thwarting IL-1β maturation by interfering with NLRP3 inflammasome assembly [90][91][92], which is crucial for innate immune sensing and coordination [93]. An IAV-mediated nullification of IL-1β secretion would be of dramatic consequences during streptococcal superinfections.…”

Section: Discussionmentioning

confidence: 99%

Influenza A Virus Exacerbates Group A Streptococcus Infection and Thwarts Anti-bacterial Inflammatory Responses in Murine Macrophages

Volzke

Brendel

Weipert

et al. 2022

Preprint

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Seasonal influenza epidemics pose a considerable hazard for global health. In the past decades, accumulating evidence revealed that influenza A virus (IAV) renders the host vulnerable to bacterial superinfections which in turn are a major cause for morbidity and mortality. However, whether the impact of influenza on anti-bacterial innate immunity is restricted to the vicinity of the lung or systemically extends to remote sites is underexplored. We therefore sought to investigate intranasal infection of adult C57BL/6J mice with IAV H1N1 in combination with bacteremia elicited by intravenous application of Group A Streptococcus (GAS). Co-infection in vivo was supplemented in vitro by challenging murine bone marrow derived macrophages and exploring gene expression and cytokine secretion. Our results show that viral infection of mice caused mild disease, led to persistent pulmonary immune response in the lung and induced the depletion of CCL2 in the periphery. Influenza preceding GAS infection promoted the unopposed dissemination of bacteria and their invasion into remote tissues like lung and joints and was accompanied by exacerbated sepsis. In vitro co-infection of macrophages led to significantly elevated expression of TLR2 and CD80 compared to bacterial mono-infection, whereas CD163 and CD206 were downregulated. The GAS-inducible upregulation of inflammatory genes, such as Nos2, as well as the secretion of TNFα and IL-1β were notably reduced or even abrogated following co-infection. Our results indicate that IAV primes an innate immune layout that is inadequately equipped for bacterial clearance.

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“…In addition, some viruses have developed strategies to evade the host innate immune response that involve the activation of various pattern recognition receptors (PRRs), including toll-like receptors (TLRs), among others, and the subsequent signaling resulting in the production of proinflammatory cytokines and/or the activation of programmed cell death [ 114 , 117 , 118 , 120 , 127 , 128 , 129 ]. For example, IAV is recognized by various PRRs, depending on the cellular compartment, the different types of cells, and the different stages of infection [ 130 ], and may also trigger PRR activation mechanisms to subvert the innate immune response [ 131 , 132 ]. Indeed, TRL activation leading to autophagy and apoptosis is subverted by IAV to enhance virion stability [ 133 , 134 , 135 ] and to facilitate its replication [ 136 ].…”

Section: Aid Of Cathepsins To Viruses In the Host Cell Infectionmentioning

confidence: 99%

The Key Role of Lysosomal Protease Cathepsins in Viral Infections

Scarcella

d’Angelo

Ciampa

et al. 2022

IJMS

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Cathepsins encompass a family of lysosomal proteases that mediate protein degradation and turnover. Although mainly localized in the endolysosomal compartment, cathepsins are also found in the cytoplasm, nucleus, and extracellular space, where they are involved in cell signaling, extracellular matrix assembly/disassembly, and protein processing and trafficking through the plasma and nuclear membrane and between intracellular organelles. Ubiquitously expressed in the body, cathepsins play regulatory roles in a wide range of physiological processes including coagulation, hormone secretion, immune responses, and others. A dysregulation of cathepsin expression and/or activity has been associated with many human diseases, including cancer, diabetes, obesity, cardiovascular and inflammatory diseases, kidney dysfunctions, and neurodegenerative disorders, as well as infectious diseases. In viral infections, cathepsins may promote (1) activation of the viral attachment glycoproteins and entry of the virus into target cells; (2) antigen processing and presentation, enabling the virus to replicate in infected cells; (3) up-regulation and processing of heparanase that facilitates the release of viral progeny and the spread of infection; and (4) activation of cell death that may either favor viral clearance or assist viral propagation. In this review, we report the most relevant findings on the molecular mechanisms underlying cathepsin involvement in viral infection physiopathology, and we discuss the potential of cathepsin inhibitors for therapeutical applications in viral infectious diseases.

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How Influenza A Virus NS1 Deals with the Ubiquitin System to Evade Innate Immunity

Cited by 17 publications

References 347 publications

Suppression of Interferon Stimulated Genes Enhance Viral Replication of Seasonal Influenza A Virus through the JAK/STAT pathway

Suppression of Interferon Stimulated Genes Enhance Viral Replication of Seasonal Influenza A Virus through the JAK/STAT pathway

Influenza A Virus Exacerbates Group A Streptococcus Infection and Thwarts Anti-bacterial Inflammatory Responses in Murine Macrophages

The Key Role of Lysosomal Protease Cathepsins in Viral Infections

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