HTLV-1 evades type I IFN signaling by inducing the suppressor of cytokine signaling: “ SOCS-1”

Cytokine ◽  
2009 ◽  
Vol 48 (1-2) ◽  
pp. 66
Author(s):  
Stephanie Oliere ◽  
Meztli Arguello ◽  
Thi Lien-AnhNguyen ◽  
Edouardo Hernandez ◽  
Agnes Lezin ◽  
...  
Keyword(s):  
Cytokine Signaling ◽  
Type I ◽  
Type I Ifn ◽  
Suppressor Of Cytokine Signaling

scholarly journals Listeria exploits IFITM3 to suppress antibacterial activity in phagocytes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joel M. J. Tan ◽  
Monica E. Garner ◽  
James M. Regeimbal ◽  
Catherine J. Greene ◽  
Jorge D. Rojas Márquez ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Transmembrane Protein ◽  
Foodborne Pathogen ◽  
Systemic Infection ◽  
Cytokine Signaling ◽  
Type I ◽  
Type I Ifn ◽  
Antiviral Protein

AbstractThe type I interferon (IFN) signaling pathway has important functions in resistance to viral infection, with the downstream induction of interferon stimulated genes (ISG) protecting the host from virus entry, replication and spread. Listeria monocytogenes (Lm), a facultative intracellular foodborne pathogen, can exploit the type I IFN response as part of their pathogenic strategy, but the molecular mechanisms involved remain unclear. Here we show that type I IFN suppresses the antibacterial activity of phagocytes to promote systemic Lm infection. Mechanistically, type I IFN suppresses phagosome maturation and proteolysis of Lm virulence factors ActA and LLO, thereby promoting phagosome escape and cell-to-cell spread; the antiviral protein, IFN-induced transmembrane protein 3 (IFITM3), is required for this type I IFN-mediated alteration. Ifitm3−/− mice are resistant to systemic infection by Lm, displaying decreased bacterial spread in tissues, and increased immune cell recruitment and pro-inflammatory cytokine signaling. Together, our findings show how an antiviral mechanism in phagocytes can be exploited by bacterial pathogens, and implicate IFITM3 as a potential antimicrobial therapeutic target.

Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice

2016 ◽  
Vol 26 (1) ◽  
Author(s):  
Amira Alkharusi ◽  
Mercedes Mirecki-Garrido ◽  
Zuheng Ma ◽  
Fahad Zadjali ◽  
Amilcar Flores-Morales ◽  
...  
Keyword(s):  
Type I Diabetes ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Type I ◽  
Suppressor Of Cytokine Signaling ◽  
Β Cell ◽  
Diabetes In Mice ◽  
Socs Proteins ◽  
Stat Pathway

AbstractDiabetes type 1 is characterized by the failure of beta cells to produce insulin. Suppressor of cytokine signaling (SOCS) proteins are important regulators of the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. Previous studies have shown that GH can prevent the development of type I diabetes in mice and that SOCS2 deficiency mimics a state of increased GH sensitivity.The elevated sensitivity of SOCS2We show that 6-month-old SOCS2Knockdown of SOCS2 makes mice less sensitive to MLDSTZ. These results are consistent with the proposal that elimination of SOCS2 in pancreatic islets creates a state of β-cell hypersensitivity to GH/PRL that mimics events in pregnancy, and which is protective against MLDSTZ-induced type I diabetes in mice. SOCS2-dependent control of β-cell survival may be of relevance to islet regeneration and survival in transplantation.

scholarly journals Suppressor of Cytokine Signaling 3 Suppresses Hepatitis C Virus Replication in an mTOR-Dependent Manner

2010 ◽  
Vol 84 (12) ◽  
pp. 6060-6069 ◽  
Author(s):  
Run-Xuan Shao ◽  
Leiliang Zhang ◽  
Lee F. Peng ◽  
Eileen Sun ◽  
Woo Jin Chung ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Full Length ◽  
Cytokine Signaling ◽  
Type I ◽  
Dependent Manner ◽  
Suppressor Of Cytokine Signaling ◽  
Protein Levels ◽  
Infected Cells ◽  
Ifn Treatment

ABSTRACT We and others have observed that hepatic levels of suppressor of cytokine signaling 3 (SOCS3) are significantly higher in persons with chronic hepatitis C, particularly those who are nonresponders to interferon (IFN) treatment, than in healthy individuals. However, the relationship between SOCS3 and hepatitis C virus (HCV) replication remains unclear. Given its putative role, we hypothesized that SOCS3 is permissive for viral replication. We therefore used the OR6 cell line, which harbors a genotype 1b full-length HCV replicon, and the genotype 2a full-length HCV strain JFH1 infection system to analyze the effects of SOCS3 overexpression and short hairpin RNA (shRNA)-mediated knockdown on HCV replication. We further analyzed the role of mTOR in the effects of SOCS3 by treating selected cells with rapamycin. OR6 cells and JFH1-infected Huh7.5.1 cells expressed significantly less SOCS3 than control cells. Furthermore, inhibition of HCV replication with the HCV protease inhibitor BILN 2061 restored SOCS3 protein levels. SOCS3 overexpression in OR6 cells and JFH1-infected Huh7.5.1 cells resulted in significantly lower HCV replication than that in the control cells, despite SOCS3-related inhibition of STAT1 phosphorylation and type I IFN signaling. In contrast, JFH1-infected cells with stable SOCS3 knockdown expressed higher levels of HCV proteins and RNA than did control cells. SOCS3-targeting shRNA also knocked down mTOR and phospho-mTOR. The mTOR inhibitor rapamycin reversed the inhibitory effects of SOCS3. In independent investigations, SOCS3 unexpectedly suppressed HCV replication in an mTOR-dependent manner. These findings suggest that increased SOCS3 levels consistently observed in chronic IFN nonresponders may reflect a compensatory host antiviral response to persistent infection and that manipulation of SOCS3/mTOR may offer benefit against HCV infection.

scholarly journals Influenza A virus antagonizes type I and type II interferon responses via SOCS1-dependent ubiquitination and degradation of JAK1

2020 ◽  
Author(s):  
Yinping Du ◽  
Fan Yang ◽  
Qiuxia Wang ◽  
Nuo Xu ◽  
Yizhang Xie ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Innate Immune ◽  
Cytokine Signaling ◽  
Type I ◽  
Type Ii ◽  
Innate Immune Responses ◽  
Suppressor Of Cytokine Signaling ◽  
Interferon Responses ◽  
Socs Protein

Abstract BACKGROUND Although influenza A virus (IAV) employs diverse strategies to evade IFN responses by inhibiting the synthesis of IFN, how IAV regulates signaling downstream of IFN is incompletely understood. METHODS In this study, we used Western blot-based protein analysis coupled with RT-qPCR, overexpression and RNA interference to investigate the regulation of JAK1 by IAV infection. RESULTS The results indicated that JAK1 was ubiquitinated and degraded, resulting in inhibition of type I and type II IFN responses, demonstrating that IAV antagonizes the IFN-activated JAK/STAT signaling pathway by inducing the degradation of JAK1. Furthermore. IAV infection upregulated the suppressor of cytokine signaling (SOCS) protein SOCS1, and SOCS1 mediated the ubiquitination and degradation of JAK1. CONCLUSION: Collectively, our findings suggest that IAV infection induced SOCS1 expression promotes JAK1 degradation, which in turn inhibits host innate immune responses.

scholarly journals Suppressor of Cytokine Signaling (SOCS) 1 Inhibits Type I Interferon (IFN) Signaling via the Interferon α Receptor (IFNAR1)-associated Tyrosine Kinase Tyk2

2011 ◽  
Vol 286 (39) ◽  
pp. 33811-33818 ◽  
Author(s):  
Rebecca A. R. Piganis ◽  
Nicole A. De Weerd ◽  
Jodee A. Gould ◽  
Christian W. Schindler ◽  
Ashley Mansell ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Type I Interferon ◽  
Cytokine Signaling ◽  
Interferon Α ◽  
Type I ◽  
Suppressor Of Cytokine Signaling

scholarly journals Influenza A virus antagonizes type I and type II interferon responses via SOCS1-dependent ubiquitination and degradation of JAK1

2020 ◽  
Author(s):  
Yinping Du ◽  
Fan Yang ◽  
Qiuxia Wang ◽  
Nuo Xu ◽  
Yizhang Xie ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Innate Immune ◽  
Cytokine Signaling ◽  
Type I ◽  
Type Ii ◽  
Innate Immune Responses ◽  
Suppressor Of Cytokine Signaling ◽  
Interferon Responses ◽  
Socs Protein

Abstract BACKGROUND: Although influenza A virus (IAV) employs diverse strategies to evade IFN responses by inhibiting the synthesis of IFN, how IAV regulates signaling downstream of IFN is incompletely understood.METHODS: In this study, we used Western blot-based protein analysis coupled with RT-qPCR, overexpression and RNA interference to investigate the regulation of JAK1 by IAV infection.RESULTS: The results indicated that JAK1 was ubiquitinated and degraded, resulting in inhibition of type I and type II IFN responses, demonstrating that IAV antagonizes the IFN-activated JAK/STAT signaling pathway by inducing the degradation of JAK1. Furthermore. IAV infection upregulated the suppressor of cytokine signaling (SOCS) protein SOCS1, and SOCS1 mediated the ubiquitination and degradation of JAK1. CONCLUSION: Collectively, our findings suggest that IAV infection induces SOCS1 expression to promote JAK1 degradation, which in turn inhibits host innate immune responses.

Suppressor of cytokine signaling 1 regulates the immune response to infection by a unique inhibition of type I interferon activity

2005 ◽  
Vol 7 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Jennifer E Fenner ◽  
Robyn Starr ◽  
Ann L Cornish ◽  
Jian-Guo Zhang ◽  
Donald Metcalf ◽  
...  
Keyword(s):  
Immune Response ◽  
Type I Interferon ◽  
Cytokine Signaling ◽  
Type I ◽  
Suppressor Of Cytokine Signaling ◽  
Interferon Activity

scholarly journals JC Polyomavirus Infection of Primary Human Renal Epithelial Cells Is Controlled by a Type I IFN-Induced Response

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Benedetta Assetta ◽  
Marco De Cecco ◽  
Bethany O’Hara ◽  
Walter J. Atwood
Keyword(s):  
Epithelial Cells ◽  
Persistent Infection ◽  
Striking Difference ◽  
Cytokine Signaling ◽  
Induced Response ◽  
Type I ◽  
Type I Ifn ◽  
Infected Cells ◽  
Human Polyomaviruses

ABSTRACTThe JC and BK human polyomaviruses (JCPyV and BKPyV, respectively) establish lifelong persistent infections in the kidney. In immunosuppressed individuals, JCPyV causes progressive multifocal leukoencephalopathy (PML), a fatal neurodegenerative disease, and BKPyV causes polyomavirus-associated nephropathy (PVN). In this study, we compared JCPyV and BKPyV infections in primary human renal proximal tubule epithelial (HRPTE) cells. JCPyV established a persistent infection, but BKPyV killed the cells in 15 days. To identify the cellular factors responsible for controlling JCPyV infection and promoting viral persistence, we profiled the transcriptomes of JCPyV- and BKPyV-infected cells at several time points postinfection. We found that infection with both viruses induced interferon production but that interferon-stimulated genes (ISGs) were only activated in the JCPyV-infected cells. Phosphorylated STAT1 and IRF9, which are responsible for inducing ISGs, translocated to the nucleus of JCPyV-infected cells but did not in BKPyV-infected cells. In BKPyV-infected cells, two critical suppressors of cytokine signaling, SOCS3 and SOCS1, were induced. Infection with BKPyV but not JCPyV caused reorganization of PML bodies that are associated with inactivating antiviral responses. Blockade of the interferon receptor and neutralization of soluble interferon alpha (IFN-α) and IFN-β partially alleviated the block to JCPyV infection, leading to enhanced infectivity. Our results show that a type I IFN response contributes to the establishment of persistent infection by JCPyV in HRPTE cells.IMPORTANCEThe human polyomaviruses JCPyV and BKPyV both establish lifelong persistent infection in the kidneys. In immunosuppressed patients, BKPyV causes significant pathology in the kidney, but JCPyV is only rarely associated with disease in this organ. The reasons behind this striking difference in kidney pathology are unknown. In this study, we show that infection of primary human renal tubule epithelial cells with JCPyV and BKPyV results in divergent innate immune responses that control JCPyV but fail to control BKPyV. This is the first study that directly compares JCPyV and BKPyV infectionin vitroin the same cell type they naturally infect, and the significant differences that have been uncovered could in part explain the distinct disease outcomes.

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