Characterization of Influenza A Virus Infection in Mouse Pulmonary Stem/Progenitor Cells

Chao, Tai‐Ling; Gu, Sing-Yi; Lin, Pei-Yu; Chou, Yu-Tien; Ling, Thai-Yen; Chang, Sui‐Yuan

doi:10.3389/fmicb.2019.02942

Cited by 8 publications

(5 citation statements)

References 51 publications

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“…These results suggest that permanent and unregulated phosphorylation at this site prohibits the generation of virus progeny. To characterize the mutations further, all rescued viruses with mutations in the polymerase subunits were investigated for their replication in mouse lung epithelial cells (MLE-15), which are widely used to study SC35M infection 33 , 34 . A comparative analysis of mutant viruses in multi-cycle replication assays showed roughly similar replication kinetics at 12, 24, and 36 h.p.i.…”

Section: Resultsmentioning

confidence: 99%

Phosphorylation of the PA subunit of influenza polymerase at Y393 prevents binding of the 5′-termini of RNA and polymerase function

Liu

Madhugiri

Saul

et al. 2023

Sci Rep

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The influenza A virus (IAV) polymerase is a multifunctional machine that can adopt alternative configurations to perform transcription and replication of the viral RNA genome in a temporally ordered manner. Although the structure of polymerase is well understood, our knowledge of its regulation by phosphorylation is still incomplete. The heterotrimeric polymerase can be regulated by posttranslational modifications, but the endogenously occurring phosphorylations at the PA and PB2 subunits of the IAV polymerase have not been studied. Mutation of phosphosites in PB2 and PA subunits revealed that PA mutants resembling constitutive phosphorylation have a partial (S395) or complete (Y393) defect in the ability to synthesize mRNA and cRNA. As PA phosphorylation at Y393 prevents binding of the 5′ promoter of the genomic RNA, recombinant viruses harboring such a mutation could not be rescued. These data show the functional relevance of PA phosphorylations to control the activity of viral polymerase during the influenza infectious cycle.

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Section: Resultsmentioning

confidence: 99%

Phosphorylation of the PA subunit of influenza polymerase at Y393 prevents binding of the 5′-termini of RNA and polymerase function

Liu

Madhugiri

Saul

et al. 2023

Sci Rep

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“…This was observed within the BM GMP pool in this study following infection, and previously in response to allergic airways challenge (44) and in patients with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection (45). It is important to note we are currently unable to determine whether the transient reduction in lung MPPs is a direct result of active commitment, or whether such progenitors are susceptible to IAV infection, as observed with alveolar progenitors (46). Nevertheless, repopulation of lung progenitor subsets is evident upon disease resolution, with an overcompensation of GMPs, illustrating the inherent capacity of this specialised progenitor niche to re-establish homeostatic cellular population dynamics following significant local perturbation.…”

Section: Discussionmentioning

confidence: 99%

Mapping lung hematopoietic progenitors: Developmental kinetics and response to Influenza A viral infection

Mincham,

Lauzon-Joset,

Read

et al. 2023

Preprint

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The bone marrow is a specialised niche responsible for the maintenance of hematopoietic stem and progenitor cells during homeostasis and inflammation. Recent studies however have extended this essential role to the extramedullary and extravascular lung microenvironment. Here, we provide further evidence for a reservoir of hematopoietic stem and progenitor cells within the lung from embryonic day 18.5 until adulthood. These lung progenitors display distinct microenvironment-specific developmental kinetics compared to their bone marrow counterparts, exemplified by a rapid shift from a common myeloid to megakaryocyte-erythrocyte progenitor dominated niche with increasing age. In adult mice, Influenza A viral infection results in a transient reduction in multipotent progenitors within the lungs, with a parallel increase in downstream granulocyte-macrophage progenitors and dendritic cell populations associated with acute viral infections. Our findings suggest lung hematopoietic progenitors play a role in re-establishing immunological homeostasis in the respiratory mucosa, which may have significant clinical implications for maintaining pulmonary health following inflammatory perturbation.

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“…Upon pathogen infection, TLR7 interacts with its corresponding ligands, and the intracellular Toll/interleukin-1 receptor homology (TIR) domain of activated TLR7 binds to and interacts with the carboxyl-terminus of MyD88 [ 23 ]. Activated MyD88 then induces the phosphorylation of members of the interleukin-1 receptor-associated kinase (IRAK) family to activate TRAF6 and transmit the signal to MAPK, JNK, and p65 NF- κ B [ 24 ], ultimately resulting in the secretion of many types of immune-associated cytokines and chemokines for the antiviral response, such as IFN- β and IL-6 [ 25 , 26 ]. Previous studies have found that the expression of TLR7 was significantly upregulated in immune cells infected with the influenza A virus [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Screening of Antiviral Components of Yinhuapinggan Granule and Protective Effects of Yinhuapinggan Granule on MDCK Cells with Influenza A/H1N1 Virus

Chen

Zhou

et al. 2022

BioMed Research International

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Background. Traditional Chinese medicine Yinhuapinggan granule (YHPG) has been used for treating upper respiratory tract infection like influenza, cough, and viral pneumonia. However, its active ingredients that really exert the main efficacy have not been well elucidated. This study is aimed at screening its antiviral components and investigating the potential therapeutic mechanisms of YHPG against the influenza A/PR8/34 (H1N1) virus in Madin Darby canine kidney (MDCK). Methods. MDCK cells were infected with the influenza virus and then treated with ribavirin, YHPG, and main active ingredients in YHPG. Based on the maximum nontoxic concentration (TC0), half-maximal toxic concentration (TC50), half-maximal inhibitory concentration (IC50), and therapeutic index (TI), interferon-β (IFN-β) and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the gene expression of TLR7, MyD88, tumor necrosis factor receptor-associated factor 6 (TRAF6), c-Jun amino terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK), and p65 nuclear transcription factor-kappa B (p65 NF-κB) was quantified using reverse transcription-polymerase chain reaction (RT-PCR). Results. The results indicated that the components of YHPG, such as ephedrine hydrochloride, pseudoephedrine hydrochloride, chlorogenic acid, and emodin, had significant antiviral effects. High and medium doses of YHPG effectively reduced the cytopathic effect (CPE) and significantly decreased IFN-β and IL-6 levels in the supernatant. Simultaneously, the transcript levels of TLR7, MyD88, TRAF6, JNK, p38 MAPK, and p65 NF-κB decreased in infected MDCK cells. Moreover, a certain dose-dependent relationship among different groups of YHPG was observed. Conclusions. These results indicated that YHPG and the components of YHPG had a significant inhibitory function on the proliferation of the H1N1 virus. The mechanism might be associated with suppressing the activation of the TLR7/MyD88 signaling pathway, a decrease in the mRNA expression of key target genes, and inhibition of IFN-β and IL-6 secretion.

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Characterization of Influenza A Virus Infection in Mouse Pulmonary Stem/Progenitor Cells

Cited by 8 publications

References 51 publications

Phosphorylation of the PA subunit of influenza polymerase at Y393 prevents binding of the 5′-termini of RNA and polymerase function

Phosphorylation of the PA subunit of influenza polymerase at Y393 prevents binding of the 5′-termini of RNA and polymerase function

Mapping lung hematopoietic progenitors: Developmental kinetics and response to Influenza A viral infection

Screening of Antiviral Components of Yinhuapinggan Granule and Protective Effects of Yinhuapinggan Granule on MDCK Cells with Influenza A/H1N1 Virus

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