Zika Virus-Induction of the Suppressor of Cytokine Signaling 1/3 Contributes to the Modulation of Viral Replication

Seong, Rak Kyun; Lee, Jae Kyung; Shin, Ok Sarah

doi:10.3390/pathogens9030163

Cited by 30 publications

(26 citation statements)

References 52 publications

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“…Only a handful of studies have explored the expression kinetics of SOCS in flavivirus infected cells. Whiles SOCS1 and SOCS3 upregulation have been reported in DENV and JEV infected cells [8,10], in a recent study using the African and Asian lineages of Zika virus (ZIKV), Seong and colleagues report that there is an initial down-regulation in the mRNA levels of SOCS1 and SOCS3, as we have reported in this current study; however, they witnessed an increase in SOCS1/3 levels at 48 hpi, which further declined thereafter [27]. Again, in corroboration of our results, using an unrelated virus-Enterovirus 71-Gao and colleagues show that the mRNA and protein level (by Western blot) of SOCS1 is reduced early in infected RD cells (human rhabdosarcoma) but increases at 24hpi, although not significantly [28].…”

Section: Discussionsupporting

confidence: 55%

Yellow Fever Virus Down-Regulates mRNA Expression of SOCS1 in the Initial Phase of Infection in Human Cell Lines

Yakass

Franco

Quaye

2020

Viruses

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Flaviviruses are constantly evolving diverse immune evasion strategies, and the exploitation of the functions of suppressors of cytokine signalling (SOCS) and protein inhibitors of activated STATs (PIAS) to favour virus replication has been described for Dengue and Japanese encephalitis viruses but not for yellow fever virus (YFV), which is still of global importance despite the existence of an effective vaccine. Some mechanisms that YFV employs to evade host immune defence has been reported, but the expression patterns of SOCS and PIAS in infected cells is yet to be determined. Here, we show that SOCS1 is down-regulated early in YFV-infected HeLa and HEK 293T cells, while SOCS3 and SOCS5 are not significantly altered, and PIAS mRNA expression appears to follow a rise-dip pattern akin to circadian-controlled genes. We also demonstrate that YFV evades interferon-β application to produce comparable viral titres. This report provides initial insight into the in vitro expression dynamics of SOCS and PIAS upon YFV infection and a basis for further investigation into SOCS/PIAS expression and how these modulate the immune response in animal models.

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Section: Discussionsupporting

confidence: 55%

Yellow Fever Virus Down-Regulates mRNA Expression of SOCS1 in the Initial Phase of Infection in Human Cell Lines

Yakass

Franco

Quaye

2020

Viruses

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“…Recently, SOCS proteins have gained attention as frequent targets of viral exploitation of the host immune response. Multiple viruses promote their survival by inducing SOCS1 and/or SOCS3 protein expression following infection [44][45][46][47][48][49][50][51][52]. Here, for the first time, we show that IFN-γ activation followed by CVB3 infection can result in the upregulation of SOCS expression in hNPCs and SOCS overexpression facilitates CVB3 replication.…”

Section: Discussionmentioning

confidence: 69%

Coxsackievirus B3 Infection of Human Neural Progenitor Cells Results in Distinct Expression Patterns of Innate Immune Genes

Gim

Lee

et al. 2020

Viruses

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Coxsackievirus B3 (CVB3), a member of Picornaviridae family, is an important human pathogen that causes a wide range of diseases, including myocarditis, pancreatitis, and meningitis. Although CVB3 has been well demonstrated to target murine neural progenitor cells (NPCs), gene expression profiles of CVB3-infected human NPCs (hNPCs) has not been fully explored. To characterize the molecular signatures and complexity of CVB3-mediated host cellular responses in hNPCs, we performed QuantSeq 3′ mRNA sequencing. Increased expression levels of viral RNA sensors (RIG-I, MDA5) and interferon-stimulated genes, such as IFN-β, IP-10, ISG15, OAS1, OAS2, Mx2, were detected in response to CVB3 infection, while IFN-γ expression level was significantly downregulated in hNPCs. Consistent with the gene expression profile, CVB3 infection led to enhanced secretion of inflammatory cytokines and chemokines, such as interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1). Furthermore, we show that type I interferon (IFN) treatment in hNPCs leads to significant attenuation of CVB3 RNA copy numbers, whereas, type II IFN (IFN-γ) treatment enhances CVB3 replication and upregulates suppressor of cytokine signaling 1/3 (SOCS) expression levels. Taken together, our results demonstrate the distinct molecular patterns of cellular responses to CVB3 infection in hNPCs and the pro-viral function of IFN-γ via the modulation of SOCS expression.

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“…Respiratory syncytial virus infection upregulates genes in the cytokine signal suppressor (SOCS) family that use a feedback loop to prevent antiviral signaling pathway, which is based on type I interferon. The upregulation of SOCS2 and SOCS3 gene was induced in lung epithelial cells infected with the Zika virus ( Liu et al, 2019 ; Seong et al, 2020 ). It is thought this upregulation of SOCS in response to the Zika virus regulated viral replication, possibly via the regulation of antiviral innate immune responses.…”

Section: Discussionmentioning

confidence: 99%

Integrative transcriptomics analysis of lung epithelial cells and identification of repurposable drug candidates for COVID-19

Islam

Rahman

Aydın

et al. 2020

European Journal of Pharmacology

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease, more commonly COVID-19 has emerged as a world health pandemic. There are couples of treatment methods for COVID-19, however, well-established drugs and vaccines are urgently needed to treat the COVID-19. The new drug discovery is a tremendous challenge; repurposing of existing drugs could shorten the time and expense compared with de novo drug development. In this study, we aimed to decode molecular signatures and pathways of the host cells in response to SARS-CoV-2 and the rapid identification of repurposable drugs using bioinformatics and network biology strategies. We have analyzed available transcriptomic RNA-seq COVID-19 data to identify differentially expressed genes (DEGs). We detected 177 DEGs specific for COVID-19 where 122 were upregulated and 55 were downregulated compared to control (FDR<0.05 and logFC ≥ 1). The DEGs were significantly involved in the immune and inflammatory response. The pathway analysis revealed the DEGs were found in influenza A, measles, cytokine signaling in the immune system, interleukin-4, interleukin −13, interleukin −17 signaling, and TNF signaling pathways. Protein-protein interaction analysis showed 10 hub genes (BIRC3, ICAM1, IRAK2, MAP3K8, S100A8, SOCS3, STAT5A, TNF, TNFAIP3, TNIP1). The regulatory network analysis showed significant transcription factors (TFs) that target DEGs, namely FOXC1, GATA2, YY1, FOXL1, NFKB1. Finally, drug repositioning analysis was performed with these 10 hub genes and showed that in silico validated three drugs with molecular docking. The transcriptomics signatures, molecular pathways, and regulatory biomolecules shed light on candidate biomarkers and drug targets which have potential roles to manage COVID-19. ICAM1 and TNFAIP3 were the key hubs that have demonstrated good binding affinities with repurposed drug candidates. Dabrafenib, radicicol, and AT-7519 were the top-scored repurposed drugs that showed efficient docking results when they tested with hub genes. The identified drugs should be further evaluated in molecular level wet-lab experiments in prior to clinical studies in the treatment of COVID-19.

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Zika Virus-Induction of the Suppressor of Cytokine Signaling 1/3 Contributes to the Modulation of Viral Replication

Cited by 30 publications

References 52 publications

Yellow Fever Virus Down-Regulates mRNA Expression of SOCS1 in the Initial Phase of Infection in Human Cell Lines

Yellow Fever Virus Down-Regulates mRNA Expression of SOCS1 in the Initial Phase of Infection in Human Cell Lines

Coxsackievirus B3 Infection of Human Neural Progenitor Cells Results in Distinct Expression Patterns of Innate Immune Genes

Integrative transcriptomics analysis of lung epithelial cells and identification of repurposable drug candidates for COVID-19

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