Pro-Inflammatory Cytokines and Interferon-Stimulated Gene Responses Induced by Seasonal Influenza A Virus with Varying Growth Capabilities in Human Lung Epithelial Cell Lines

Hinay, Alfredo A.; Kakee, Sosuke; Kageyama, Seiji; Tsuneki-Tokunaga, Akeno; Perdana, Waldy Y.; Akena, Yui; Nishiyama, Shota; Kanai, Koomi

doi:10.3390/vaccines10091507

Cited by 4 publications

(4 citation statements)

References 39 publications

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“…To assess the role of more downregulated ISGs in sMDCK cells, we tested the effect of the suppression of JAK/STAT signaling by adding pyridone 6 (P6) during infection. P6 is a pan-JAK inhibitor and was verified to inhibit ISG expression through competitively binding to JAK1, JAK2, JAK3, and Tyk2 [ 32 , 42 , 43 , 44 ]. ISG expression levels were examined in P6-treated aMDCK and sMDCK cells.…”

Section: Resultsmentioning

confidence: 99%

Reduction in Interferon-Stimulated Genes Contributes to High-Yield Production of Influenza Virus in Suspension MDCK Cells

Wang,

Luo,

et al. 2024

Vaccines

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Compared with the traditional vaccine produced in embryonated chicken eggs, cell-based manufacturing represented by the Madin–Darby canine kidney (MDCK) cell line has a larger production scale and reduces the risk of egg shortage in a pandemic. Establishing a culture system that enables high production of the influenza virus is a key issue in influenza vaccine production. Here, a serum-free suspension culture of MDCK (sMDCK) cells was obtained from adherent MDCK (aMDCK) cells by direct adaptation. Viral infection experiments showed that viral yields of influenza A/B virus in sMDCK cells were higher than in aMDCK cells. Transcriptome analysis revealed that numerous interferon-stimulated genes (ISGs) exhibited reduced expression in sMDCK cells. To further clarify the mechanism of high viral production in sMDCK cells, we demonstrated the antiviral role of RIG-I and IFIT3 in MDCK cells by knockdown and overexpression experiments. Furthermore, suppression of the JAK/STAT pathway enhances the viral accumulation in aMDCK cells instead of sMDCK cells, suggesting the reduction in the JAK/STAT pathway and ISGs promotes viral replication in sMDCK cells. Taken together, we elucidate the relationship between the host innate immune response and the high viral productive property of sMDCK cells, which helps optimize cell production processes and supports the production of cell-based influenza vaccines.

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Section: Resultsmentioning

confidence: 99%

Reduction in Interferon-Stimulated Genes Contributes to High-Yield Production of Influenza Virus in Suspension MDCK Cells

Wang,

Luo,

et al. 2024

Vaccines

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“…ISG15 plays a central role in host antiviral response [ 39 ]. In the case of influenza A virus infection, ISG-15 affects viral genome replication [ 40 ]. HNRNPH1 is an RNA-binding protein that forms complexes with heterogeneous nuclear RNA and participates in RNA editing, modification, and stability [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Salivary Biomarkers to Differentiate between Streptococcus pneumoniae and Influenza A Virus-Related Pneumonia in Children

et al. 2023

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Community-acquired pneumonia (CAP) is common among children and can be fatal in certain conditions. In children, CAP can be caused by viral or bacterial infections. Identification of pathogens can help select appropriate therapeutic strategies. Salivary analysis may be a potential diagnostic tool because it is noninvasive, patient-friendly, and easy to perform in children. A prospective study was conducted in children with pneumonia admitted to a hospital. Salivary samples from patients with definite Streptococcus pneumoniae and influenza A strains were used for gel-free (isobaric tag for relative and absolute quantitation (iTRAQ)) proteomics. No statistically significant difference was detected in salivary CRP levels between Streptococcus pneumoniae and influenza A pneumonia in children. Several potential salivary biomarkers were identified using gel-free iTRAQ proteomics to differentiate pneumonia from Streptococcus pneumoniae or influenza A virus infections in pediatric patients. ELISA validated that Streptococcus pneumoniae group has a higher abundance of salivary alpha 1-antichymotrypsin than those in the influenza A group. Whether these salivary biomarkers can be used to distinguish other bacteria from viral pneumonia requires further verification.

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“…This upregulation could indicate that asymptomatic patients quickly recognized and responded to the virus with the help of plasmablast cells in the extrafollicular pathway. A recent study by Hinai et al (2022) (50) has shown that an increase in the expression of interferon stimulated genes reduces the viral copies of influenza A virus in vitro. The upregulation in interferon stimulated genes in asymptomatic COVID-19 patients was also found in other studies and was correlated with good clinical outcomes in these patients (51; 52).…”

Section: Discussionmentioning

confidence: 99%

Different B cell activation patterns in asymptomatic and symptomatic COVID-19 patients

Pham

Talih

Ehrhart³

et al. 2022

Preprint

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Early and persistent defects in B cell subsets such as memory B cells were shown to be correlated with poor outcomes in COVID-19 patients. This research aimed to develop a molecular pathway model to understand the B cell development in COVID-19. A B cell transcriptomics dataset, obtained from COVID-19 patients, was analyzed on the resulting pathway model to study B cell activation. The pathway showed two distinct gene expression profiles between asymptomatic and symptomatic patients. In asymptomatic patients, there is an increase in transcript levels of antiviral interferon-stimulated genes such as ISG15, IFITM1, and NEAT1 and a driving gene for the extrafollicular pathway CXCR4 indicating a formation of plasmablast. In symptomatic patients, the results suggest an inhibition occurring at the germinal center hinting at a reduction in memory B cell production. Transcripts of driver gene CXCR5 involved in germinal center development is one of the most downregulated genes. This could contribute to the shortage in the formation of memory B cells in COVID-19. Concluding, in SARS-CoV-2 infection, B cells follow different activation routes in asymptomatic and symptomatic patients. In this study, we constructed a pathway that allowed us to analyze and interpret activation patterns of B cells in COVID-19 patients and their link to disease severity. Importantly, the pathway and approach can be reused for further research in COVID-19 or other diseases.

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Pro-Inflammatory Cytokines and Interferon-Stimulated Gene Responses Induced by Seasonal Influenza A Virus with Varying Growth Capabilities in Human Lung Epithelial Cell Lines

Cited by 4 publications

References 39 publications

Reduction in Interferon-Stimulated Genes Contributes to High-Yield Production of Influenza Virus in Suspension MDCK Cells

Reduction in Interferon-Stimulated Genes Contributes to High-Yield Production of Influenza Virus in Suspension MDCK Cells

Salivary Biomarkers to Differentiate between Streptococcus pneumoniae and Influenza A Virus-Related Pneumonia in Children

Different B cell activation patterns in asymptomatic and symptomatic COVID-19 patients

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