Downregulation of A20 Expression Increases the Immune Response and Apoptosis and Reduces Virus Production in Cells Infected by the Human Respiratory Syncytial Virus

Martín-Vicente, María; González-Sanz, Rubén; Cuesta, Isabel; Monzón, Sara; Resino, Salvador; Martı́nez, Isidoro

doi:10.3390/vaccines8010100

Cited by 12 publications

(15 citation statements)

References 74 publications

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“…ICAM1 and VCAM1 could receive signals from both MAPK and NF-kB pathways for expression ( Taniguchi and Karin, 2018 ), and contribute to neuron adhesion, stability of extracellular matrix, and permeability of brain barriers. TNFAIP3 (A20) is involved in negative regulation of inflammatory response and apoptosis, and heterozygosity of this gene causes an exacerbated cognitive impairment under inflammatory conditions ( Daems et al, 2020 ; Martín-Vicente et al, 2020 ). The primary function of CCL2 and CXCL10 is chemokines for monocytes and macrophages, but also could indirectly cause neuronal dysfunction through the recruited immune cells ( Lehmann et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Early Transcriptional Changes in Rabies Virus-Infected Neurons and Their Impact on Neuronal Functions

et al. 2021

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Rabies is a zoonotic disease caused by rabies virus (RABV). As rabies advances, patients develop a variety of severe neurological symptoms that inevitably lead to coma and death. Unlike other neurotropic viruses that can induce symptoms of a similar range, RABV-infected post-mortem brains do not show significant signs of inflammation nor the structural damages on neurons. This suggests that the observed neurological symptoms possibly originate from dysfunctions of neurons. However, many aspects of neuronal dysfunctions in the context of RABV infection are only partially understood, and therefore require further investigation. In this study, we used differentiated neurons to characterize the RABV-induced transcriptomic changes at the early time-points of infection. We found that the genes modulated in response to the infection are particularly involved in cell cycle, gene expression, immune response, and neuronal function-associated processes. Comparing a wild-type RABV to a mutant virus harboring altered matrix proteins, we found that the RABV matrix protein plays an important role in the early down-regulation of host genes, of which a significant number is involved in neuronal functions. The kinetics of differentially expressed genes (DEGs) are also different between the wild type and mutant virus datasets. The number of modulated genes remained constant upon wild-type RABV infection up to 24 h post-infection, but dramatically increased in the mutant condition. This result suggests that the intact viral matrix protein is important to control the size of host gene modulation. We then examined the signaling pathways previously studied in relation to the innate immune responses against RABV, and found that these pathways contribute to the changes in neuronal function-associated processes. We further examined a set of regulated genes that could impact neuronal functions collectively, and demonstrated in calcium imaging that indeed the spontaneous activity of neurons is influenced by RABV infection. Overall, our findings suggest that neuronal function-associated genes are modulated by RABV early on, potentially through the viral matrix protein-interacting signaling molecules and their downstream pathways.

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Section: Resultsmentioning

confidence: 99%

Early Transcriptional Changes in Rabies Virus-Infected Neurons and Their Impact on Neuronal Functions

et al. 2021

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“…In later stages of infection, this improved protection may be associated with suppression of CCL2 expression and modulation of pulmonary cytotoxic T cell [ 79 ]. A study on RSV-infected cells showed that down-regulation of A20 can increase apoptosis and induce an innate immune response in infected epithelial cells [ 80 ]. Zinc exerts an inhibitory effect on the activation of NF-kB by inducing the A20.…”

Section: Resultsmentioning

confidence: 99%

Zinc and Respiratory Viral Infections: Important Trace Element in Anti-viral Response and Immune Regulation

Sadeghsoltani

Mohammadzadeh

Safari

et al. 2021

Biol Trace Elem Res

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Influenza viruses, respiratory syncytial virus (RSV), and SARS-COV2 are among the most dangerous respiratory viruses. Zinc is one of the essential micronutrients and is very important in the immune system. The aim of this narrative review is to review the most interesting findings about the importance of zinc in the anti-viral immune response in the respiratory tract and defense against influenza, RSV, and SARS-COV2 infections. The most interesting findings on the role of zinc in regulating immunity in the respiratory tract and the relationship between zinc and acute respiratory distress syndrome (ARDS) are reviewed, as well. Besides, current findings regarding the relationship between zinc and the effectiveness of respiratory viruses’ vaccines are reviewed. The results of reviewed studies have shown that zinc and some zinc-dependent proteins are involved in anti-viral defense and immune regulation in the respiratory tract. It seems that zinc can reduce the viral titer following influenza infection. Zinc may reduce RSV burden in the lungs. Zinc can be effective in reducing the duration of viral pneumonia symptoms. Zinc may enhance the effectiveness of hydroxychloroquine in reducing mortality rate in COVID-19 patients. Besides, zinc has a positive effect in preventing ARDS and ventilator-induced lung damage. The relationship between zinc levels and the effectiveness of respiratory viruses’ vaccines, especially influenza vaccines, is still unclear, and the findings are somewhat contradictory. In conclusion, zinc has anti-viral properties and is important in defending against respiratory viral infections and regulating the immune response in the respiratory tract.

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“…Given that circTNFAIP3 is the most significantly dysregulated among the seven validated circRNAs ( Fig. 2A and E ), and its homologous protein TNFAIP3, encoded by the linear transcript of TNFAIP3 gene, plays an important role in inflammation, immunity, and virus infection ( 38 – 40 ), we therefore wondered if the circular transcript of TNFAIP3 would also be involved in virus infection and selected it for further exploration. Mapping analysis showed that circTNFAIP3 (ssc_circ_0025549, chr1, 29837503 to 29837812) derived from the TNFAIP3 gene is located on chromosome 1 in pigs, according to the ensemble database ( http://ensembl.org ) ( Fig.…”

Section: Resultsmentioning

confidence: 99%

A Previously Undiscovered Circular RNA, circTNFAIP3, and Its Role in Coronavirus Replication

Wang

et al. 2021

mBio

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Downregulation of A20 Expression Increases the Immune Response and Apoptosis and Reduces Virus Production in Cells Infected by the Human Respiratory Syncytial Virus

Cited by 12 publications

References 74 publications

Early Transcriptional Changes in Rabies Virus-Infected Neurons and Their Impact on Neuronal Functions

Early Transcriptional Changes in Rabies Virus-Infected Neurons and Their Impact on Neuronal Functions

Zinc and Respiratory Viral Infections: Important Trace Element in Anti-viral Response and Immune Regulation

A Previously Undiscovered Circular RNA, circTNFAIP3, and Its Role in Coronavirus Replication

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