Japanese encephalitis virus restricts HMGB1 expression to maintain MAPK pathway activation for viral replication

Xing, Jinchao; Liang, Jiaqi; Liu, Shukai; Huang, Lihong; Hu, Ping; Liu, Lele; Liao, Ming; Qi, Wenbao

doi:10.1016/j.vetmic.2021.109237

Cited by 9 publications

(3 citation statements)

References 35 publications

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“…Dengue virus exploits HMGB1-mediated autophagy to enhance virus propagation [ 54 ]. JEV activates the MAPK pathway by restricting HMGB1 expression for viral replication [ 55 ]. Hence, HMGB1 is expected to be a promising therapeutic target for viral diseases.…”

Section: Discussionmentioning

confidence: 99%

HMGB1 is involved in viral replication and the inflammatory response in coxsackievirus A16-infected 16HBE cells via proteomic analysis and identification

Liu

Yang

et al. 2023

Virol J

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Coxsackievirus A16 (CV-A16) is still an important pathogen that causes hand, foot and mouth disease (HFMD) in young children and infants worldwide. Previous studies indicated that CV-A16 infection is usually mild or self-limiting, but it was also found that CV-A16 infection can trigger severe neurological complications and even death. However, there are currently no vaccines or antiviral compounds available to either prevent or treat CV-A16 infection. Therefore, investigation of the virus‒host interaction and identification of host proteins that play a crucial regulatory role in the pathogenesis of CV-A16 infection may provide a novel strategy to develop antiviral drugs. Here, to increase our understanding of the interaction of CV-A16 with the host cell, we analyzed changes in the proteome of 16HBE cells in response to CV-A16 using tandem mass tag (TMT) in combination with LC‒MS/MS. There were 6615 proteins quantified, and 172 proteins showed a significant alteration during CV-A16 infection. These differentially regulated proteins were involved in fundamental biological processes and signaling pathways, including metabolic processes, cytokine‒cytokine receptor interactions, B-cell receptor signaling pathways, and neuroactive ligand‒receptor interactions. Further bioinformatics analysis revealed the characteristics of the protein domains and subcellular localization of these differentially expressed proteins. Then, to validate the proteomics data, 3 randomly selected proteins exhibited consistent changes in protein expression with the TMT results using Western blotting and immunofluorescence methods. Finally, among these differentially regulated proteins, we primarily focused on HMGB1 based on its potential effects on viral replication and virus infection-induced inflammatory responses. It was demonstrated that overexpression of HMGB1 could decrease viral replication and upregulate the release of inflammatory cytokines, but deletion of HMGB1 increased viral replication and downregulated the release of inflammatory cytokines. In conclusion, the results from this study have helped further elucidate the potential molecular pathogenesis of CV-A16 based on numerous protein changes and the functions of HMGB1 Found to be involved in the processes of viral replication and inflammatory response, which may facilitate the development of new antiviral therapies as well as innovative diagnostic methods.

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Section: Discussionmentioning

confidence: 99%

HMGB1 is involved in viral replication and the inflammatory response in coxsackievirus A16-infected 16HBE cells via proteomic analysis and identification

Liu

Yang

et al. 2023

Virol J

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“…However, in the recent years, it was reported that potentially participates in the regulation of viral replication cycles with complicated mechanisms [10]. For example, Japanese encephalitis virus restricts HMGB1 expression to maintain MAPK pathway activation for viral replication [40]. HMGB1 promotes hepatitis C virus replication by interaction with stem-loop 4 in the viral 5'-untranslated region [42].…”

Section: Discussionmentioning

confidence: 99%

Tandem mass tag (TMT) labeling-based quantitative proteomic analysis reveals the cellular protein characteristics of 16HBE cells infected with coxsackievirus A10 and the potential effect of HMGB1 on viral replication

Song,

Zhao,

et al. 2023

Arch Virol

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Coxsackievirus A10 (CV-A10) is recognized as one of the most important pathogens associated with hand, foot, and mouth disease (HFMD) in young children under 5 years of age worldwide, and it can lead to fatal neurological complications. However, available commercial vaccines fail to protect against CV-A10. Therefore, the study of new protein targets against CV-A10 highlight the urgent need for the development of vaccine-based strategies. Currently, advances in proteomics have enabled a comprehensive understanding of host-pathogen interactions in recent years. Here, to study CV-A10-host interaction, a global quantitative proteomic analysis could help uncover the molecular determinants of host cellular proteins and excavate key host proteins following CV-A10 infection. Through tandem mass tagging (TMT)-based mass spectrometry, it was found that a total of 6615 host proteins were quanti ed, with 293 proteins being differentially regulated. To ensure the validity and reliability of the proteomics data, 3 randomly selected proteins were veri ed by Western blot analysis, and the results were consistent with the TMT results. Further functional analysis showed that the up-regulated and down-regulated proteins were individually enriched in diverse biological activities and signaling pathways, such as metabolic process, biosynthetic process, AMPK signaling pathway, Neurotrophin signaling pathway, MAPK signaling pathway, GABAergic synapse, and so on. Moreover, subsequent bioinformatics analysis further exhibited that these differentially expressed proteins contained distinct domains, localized in different subcellular components, and generated a complex network. Finally, it was also found that HMGB1 might be a key host factor to be involved in CV-A10 replication. In summary, our ndings provided comprehensive insights into the proteomic pro le during CV-A10 infection and added depth to our understanding of the relationship between CV-A10 and host cell, as well as also established a proteomic signature for this viral infection. Meanwhile, based on the effect of HMGB1 on CV-A10 replication, it might be regarded as a promising therapeutic target against CV-A10 infection.

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“…The cells were infected with a 10-fold series of the diluted viral medium. The cells were fixed with methanol at −20°C for 30 min at 48 hpi and detected by immunocytochemistry ( 62 ). The TCID 50 was determined by using the method of Reed and Muench.…”

Section: Methodsmentioning

confidence: 99%

USP1-Associated Factor 1 Modulates Japanese Encephalitis Virus Replication by Governing Autophagy and Interferon-Stimulated Genes

Xing

Che

et al. 2023

Microbiol Spectr

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Japanese encephalitis virus restricts HMGB1 expression to maintain MAPK pathway activation for viral replication

Cited by 9 publications

References 35 publications

HMGB1 is involved in viral replication and the inflammatory response in coxsackievirus A16-infected 16HBE cells via proteomic analysis and identification

HMGB1 is involved in viral replication and the inflammatory response in coxsackievirus A16-infected 16HBE cells via proteomic analysis and identification

Tandem mass tag (TMT) labeling-based quantitative proteomic analysis reveals the cellular protein characteristics of 16HBE cells infected with coxsackievirus A10 and the potential effect of HMGB1 on viral replication

USP1-Associated Factor 1 Modulates Japanese Encephalitis Virus Replication by Governing Autophagy and Interferon-Stimulated Genes

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