Influenza A Virus Nucleoprotein Activates the JNK Stress-Signaling Pathway for Viral Replication by Sequestering Host Filamin A Protein

Sharma, Anshika; Batra, Jyoti; Stuchlik, Olga; Reed, Matthew S.; Pohl, Jan; Chow, Vincent; Sambhara, Suryaprakash; Lal, Sunil K.

doi:10.3389/fmicb.2020.581867

Cited by 10 publications

(5 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Viral nucleoprotein hijacked cellular Filamin A, resulting in activation of the JNK pathway to promote virus e cient replication. In vivo studies demonstrated that JNK inhibition reduced virus titer and alleviated virus-mediated lung injury [39]. Our present study showed that arctiin suppressed H9N2 virus-mediated JNK activation.…”

Section: Discussionsupporting

confidence: 60%

Arctiin Suppresses H9N2 Avian Influenza Virus-Mediated Inflammation Via Activation of Nrf2/HO-1 Signaling

Zhou

Wang²,

Liang

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: H9N2 avian influenza viruses (AIVs) infect avian and mammalian hosts and provide internal genes for new emerging highly pathogenic avian viruses that cause severe pneumonia with high mortality, for which few medications are available. Arctiin, a bioactive lignan glycoside, has been reported to possess multiple pharmacological properties. However, the effect of arctiin on H9N2 virus infection is unclear. In the current study, we analyzed the effect of arctiin on H9N2 virus infection and the underlying molecular mechanism in vitro. Methods: The antiviral effect against H9N2 virus was determined by plaque reduction assay (PRA) and progeny virus reduction assay. We employed MTT assay, qRT-PCR, ELISA, immunofluorescence and Western blotting to better understand the anti-inflammatory effect and corresponding mechanism of arctiin on H9N2 virus-infected cells.Results: The results showed that arctiin had antiviral activity against H9N2 virus. Arctiin treatment reduced H9N2 virus-triggered proinflammatory cytokines, such as IL-6, and TNF-α. Moreover, arctiin significantly suppressed H9N2 virus-mediated expression of COX-2 and PGE2. Furthermore, we found that arctiin inhibited H9N2 virus-mediated activation of RIG-I/JNK MAPK signaling. Interestingly, arctiin treatment obviously reversed H9N2 virus-induced reduction of Nrf2, increased the nuclear translocation of Nrf2, and upregulated Nrf2 signaling target genes (HO-1 and SOD2). Zinc protoporphyrin (Znpp)—an HO-1 inhibitor—weakened the inhibitory effect of arctiin on H9N2 virus-induced RIG-I/JNK MAPK and proinflammatory mediators. Conclusion: Taken together, these results suggested that the anti-inflammatory effects of arctiin on H9N2 virus infection may be due to the activation of Nrf2/HO-1 and blocked RIG-I/JNK MAPK signaling; thus, arctiin may be a promising agent for prevention and treatment of H9N2 virus infections.

show abstract

Section: Discussionsupporting

confidence: 60%

Arctiin Suppresses H9N2 Avian Influenza Virus-Mediated Inflammation Via Activation of Nrf2/HO-1 Signaling

Zhou

Wang²,

Liang

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Viral nucleoprotein hijacked cellular Filamin A, resulting in activation of the JNK pathway to promote virus efficient replication. In vivo studies demonstrated that JNK inhibition reduced virus titer and alleviated virus-mediated lung injury [ 42 ]. Our present study showed that arctiin suppressed H9N2 virus-mediated JNK activation.…”

Section: Discussionmentioning

confidence: 99%

Arctiin suppresses H9N2 avian influenza virus-mediated inflammation via activation of Nrf2/HO-1 signaling

Zhou

Wang²,

Liang

et al. 2021

BMC Complement Med Ther

View full text Add to dashboard Cite

Background H9N2 avian influenza viruses (AIVs) infect avian and mammalian hosts and provide internal genes for new emerging highly pathogenic avian viruses that cause severe pneumonia with high mortality, for which few medications are available. Arctiin, a bioactive lignan glycoside, has been reported to possess multiple pharmacological properties. However, the effect of arctiin on H9N2 virus infection is unclear. In the current study, we analyzed the effect of arctiin on H9N2 virus infection and the underlying molecular mechanism in vitro. Methods The antiviral effect against H9N2 virus was determined by plaque reduction assay (PRA) and progeny virus reduction assay. We employed MTT assay, qRT-PCR, ELISA, immunofluorescence and Western blotting to better understand the anti-inflammatory effect and corresponding mechanism of arctiin on H9N2 virus-infected cells. Results The results showed that arctiin had antiviral activity against H9N2 virus. Arctiin treatment reduced H9N2 virus-triggered proinflammatory cytokines, such as IL-6, and TNF-α. Moreover, arctiin significantly suppressed H9N2 virus-mediated expression of COX-2 and PGE2. Furthermore, we found that arctiin inhibited H9N2 virus-mediated activation of RIG-I/JNK MAPK signaling. Interestingly, arctiin treatment obviously reversed H9N2 virus-induced reduction of Nrf2, increased the nuclear translocation of Nrf2, and upregulated Nrf2 signaling target genes (HO-1 and SOD2). Zinc protoporphyrin (Znpp)—an HO-1 inhibitor—weakened the inhibitory effect of arctiin on H9N2 virus-induced RIG-I/JNK MAPK and proinflammatory mediators. Conclusion Taken together, these results suggested that the anti-inflammatory effects of arctiin on H9N2 virus infection may be due to the activation of Nrf2/HO-1 and blocked RIG-I/JNK MAPK signaling; thus, arctiin may be a promising agent for prevention and treatment of H9N2 virus infections.

show abstract

“…A549 cells were infected with H1N1 or H5N1 and incubated for 1, 5 and 8 h to investigate the cellular phosphorylation responses at various stages of IAV propagation. As a control, we prepared cell extracts that were used to test the occurrence of several well-documented phosphorylations in the activation loops of c-Jun N-terminal kinase (JNK), extracellular-signal regulated kinase (ERK) and AKT kinases by Western blot analysis [35, 36]. The results from these experiments confirmed the occurrence of virus-regulated phosphorylations that showed dynamic regulation and virus-specific kinetics ().…”

Section: Resultsmentioning

confidence: 92%

Comparative kinase activity profiling of pathogenic influenza A viruses reveals new anti- and pro-viral protein kinases

Liu

Weiß

Saul

et al. 2022

Journal of General Virology

View full text Add to dashboard Cite

Constant evolution of influenza A viruses (IAVs) leads to the occurrence of new virus strains, which can cause epidemics and occasional pandemics. Here we compared two medically relevant IAVs, namely A/Hamburg/4/09 (H1N1pdm09) of the 2009 pandemic and the highly pathogenic avian IAV human isolate A/Thailand/1(KAN-1)/2004 (H5N1), for their ability to trigger intracellular phosphorylation patterns using a highly sensitive peptide-based kinase activity profiling approach. Virus-dependent tyrosine phosphorylations of substrate peptides largely overlap between the two viruses and are also strongly overrepresented in comparison to serine/threonine peptide phosphorylations. Both viruses trigger phosphorylations with distinct kinetics by overlapping and different kinases from which many form highly interconnected networks. As approximately half of the kinases forming a signalling hub have no known function for the IAV life cycle, we interrogated selected members of this group for their ability to interfere with IAV replication. These experiments revealed negative regulation of H1N1pdm09 and H5N1 replication by NUAK [novel (nua) kinase] kinases and by redundant ephrin A (EphA) receptor tyrosine kinases.

show abstract

Influenza A Virus Nucleoprotein Activates the JNK Stress-Signaling Pathway for Viral Replication by Sequestering Host Filamin A Protein

Cited by 10 publications

References 52 publications

Arctiin Suppresses H9N2 Avian Influenza Virus-Mediated Inflammation Via Activation of Nrf2/HO-1 Signaling

Arctiin Suppresses H9N2 Avian Influenza Virus-Mediated Inflammation Via Activation of Nrf2/HO-1 Signaling

Arctiin suppresses H9N2 avian influenza virus-mediated inflammation via activation of Nrf2/HO-1 signaling

Comparative kinase activity profiling of pathogenic influenza A viruses reveals new anti- and pro-viral protein kinases

Contact Info

Product

Resources

About