Induction of SOCS Expression by EV71 Infection Promotes EV71 Replication

Gao, Wenying; Huang, Min; Liu, Xin; Li, Zhaolong; Yang, Yongjun; Zhang, Wenyan

doi:10.1155/2020/2430640

Cited by 12 publications

(9 citation statements)

References 30 publications

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“…TDRD3 in innate immunity mechanisms including degradation of IFNAR1 [31]. as well as blocking JAK-STAT signaling downstream from the receptors by induction of KPNA1 degradation [32], YTHDF3 cleavage [33], and induction of SOCS1 and SOCS3 expression (negative regulators of JAK-STAT signaling) upon infection [34]. Consistent with enteroviral-mediated JAK-STAT signaling abrogation, we noted no phosphorylated STAT1 in our infected cell lines (S1A Fig) . During viral infection, interferon and ISGs expression levels only modestly changed, however KD/KO cells generally exhibited decreased magnitudes of expression of ISG15, IFNλ1, and ISG56 compared to WT cells.…”

Section: Plos Pathogenssupporting

confidence: 74%

TDRD3 is an antiviral restriction factor that promotes IFN signaling with G3BP1

2022

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Stress granules (SGs) are highly dynamic cytoplasmic foci that form in response to activation of the integrated stress response (ISR) that results in eIF2α phosphorylation and global translation shutdown. Stress granules, which are largely nucleated by G3BP1, serve as hubs for mRNA triage, but there is mounting evidence that they also perform cell signaling functions that are vital to cell survival, particularly during viral infection. We previously showed that SG formation leads to NFκB activation and JNK signaling and that this association may be due in part to G3BP1-dependent recruitment of PKR to SGs. Others have reported close associations between G3BP1 and various innate immune PRRs of the type 1 interferon signaling system, including RIG-I. We also reported SG assembly dynamics is dependent on the arginine-methylation status of G3BP1. Another protein that rapidly localizes to SGs, TDRD3, is a methyl reader protein that performs transcriptional activation and adaptor functions within the nucleus, but neither the mechanism nor its function in SGs is clear. Here, we present evidence that TDRD3 localizes to SGs partly based upon methylation potential of G3BP1. We also characterize granules that TDRD3 forms during overexpression and show that these granules can form in the absence of G3BP but also contain translation components found in canonical SGs. We also show for the first time that SGs recruit additional interferon effectors IRF3, IRF7, TBK1, and Sting, and provide evidence that TDRD3 may play a role in recruitment of these factors. We also present evidence that TDRD3 is a novel antiviral protein that is cleaved by enteroviral 2A proteinase. G3BP1 and TDRD3 knockdown in cells results in altered transcriptional regulation of numerous IFN effectors in complex modulatory patterns that are distinctive for G3BP1 and TDRD3. Overall, we describe a novel role of TDRD3 in innate immunity in which G3BP1 and TDRD3 may coordinate to play important roles in regulation of innate antiviral defenses.

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Section: Plos Pathogenssupporting

confidence: 74%

TDRD3 is an antiviral restriction factor that promotes IFN signaling with G3BP1

2022

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“…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]. In contrast to our results, Steffensen and colleagues reported an up-regulation of SOCS1 in brain resident cells of mice infected with YF-17D via intracranial injection.…”

Section: Discussionsupporting

confidence: 91%

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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“…Also, SOCS3 is a host protein that can be employed by viruses. SOCS3 can be induced by various viruses, including NDV, DHAV-1, HIV-1 and Enterovirus 71 (EV71) (Akhtar et al, 2010;Wang et al, 2019a;Xie et al, 2019;Gao et al, 2020). SOCS3 also inhibits or promotes viral replication when acted upon by small RNA molecules (Ma et al, 2018;Wang et al, 2019b;Duan et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

SOCS3 Promotes ALV-J Virus Replication via Inhibiting JAK2/STAT3 Phosphorylation During Infection

et al. 2021

Front. Cell. Infect. Microbiol.

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Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that causes immunosuppression and neoplastic diseases in poultry. Cytokine signal-transduction inhibitor molecule 3 (SOCS3) is an important negative regulator of the JAK2/STAT3 signaling pathway and plays certain roles in ALV-J infection. It is of significance to confirm the roles of SOCS3 in ALV-J infection and study how this gene affects ALV-J infection. In this study, we assessed the expression of the SOCS3 gene in vivo and in vitro, and investigated the roles of SOCS3 in ALV-J infection using overexpressed or interfered assays with the SOCS3 in DF-1 cells. The results showed that the SOCS3 expression of ALV-J infected chickens was different from uninfected chickens in the spleen, thymus and cecal tonsil. Further, SOCS3 is mainly expressed in the nucleus as determined by immunofluorescence assay. Overexpression of SOCS3 in DF-1 cells promoted the replication of ALV-J virus, and the expression of interferons (IFNα and INFβ), inflammatory factors (IL-6 and TNFα) along with interferon-stimulating genes (CH25H, MX1, OASL, and ZAP). Conversely, interference of SOCS3 showed the opposite results. We also observed that SOCS3 promoted ALV-J virus replication by inhibiting JAK2/STAT3 phosphorylation. In conclusion, SOCS3 promotes ALV-J replication via inhibiting the phosphorylation of the JAK2/STAT3 signaling pathway. These results would advance further understanding of the persistent infection and the viral immune evasion of the ALV-J virus.

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Induction of SOCS Expression by EV71 Infection Promotes EV71 Replication

Cited by 12 publications

References 30 publications

TDRD3 is an antiviral restriction factor that promotes IFN signaling with G3BP1

TDRD3 is an antiviral restriction factor that promotes IFN signaling with G3BP1

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

SOCS3 Promotes ALV-J Virus Replication via Inhibiting JAK2/STAT3 Phosphorylation During Infection

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