scholarly journals Author response: Rotavirus VP3 targets MAVS for degradation to inhibit type III interferon expression in intestinal epithelial cells

2018 ◽  
Author(s):  
Siyuan Ding ◽  
Shu Zhu ◽  
Lili Ren ◽  
Ningguo Feng ◽  
Yanhua Song ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Author Response ◽  
Intestinal Epithelial ◽  
Type Iii ◽  
Type Iii Interferon

scholarly journals Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells

2020 ◽  
Author(s):  
Megan L. Stanifer ◽  
Carmon Kee ◽  
Mirko Cortese ◽  
Sergio Triana ◽  
Markus Mukenhirn ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
De Novo ◽  
Intestinal Epithelial Cells ◽  
Critical Role ◽  
Type I ◽  
Intestinal Epithelial ◽  
Virus Particles ◽  
Type Iii ◽  
Human Intestinal Epithelial Cells ◽  
Type Iii Interferon

SummarySARS-CoV-2 is an unprecedented worldwide health problem that requires concerted and global approaches to better understand the virus in order to develop novel therapeutic approaches to stop the COVID-19 pandemic and to better prepare against potential future emergence of novel pandemic viruses. Although SARS-CoV-2 primarily targets cells of the lung epithelium causing respiratory infection and pathologies, there is growing evidence that the intestinal epithelium is also infected. However, the importance of the enteric phase of SARS-CoV-2 for virus-induced pathologies, spreading and prognosis remains unknown. Here, using both colon-derived cell lines and primary non-transformed colon organoids, we engage in the first comprehensive analysis of SARS-CoV-2 lifecycle in human intestinal epithelial cells. Our results demonstrate that human intestinal epithelial cells fully support SARS-CoV-2 infection, replication and production of infectious de-novo virus particles. Importantly, we identified intestinal epithelial cells as the best culture model to propagate SARS-CoV-2. We found that viral infection elicited an extremely robust intrinsic immune response where, interestingly, type III interferon mediated response was significantly more efficient at controlling SARS-CoV-2 replication and spread compared to type I interferon. Taken together, our data demonstrate that human intestinal epithelial cells are a productive site of SARS-CoV-2 replication and suggest that the enteric phase of SARS-CoV-2 may participate in the pathologies observed in COVID-19 patients by contributing in increasing patient viremia and by fueling an exacerbated cytokine response.

scholarly journals Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells

Cell Reports ◽  
2020 ◽  
Vol 32 (1) ◽  
pp. 107863 ◽  
Author(s):  
Megan L. Stanifer ◽  
Carmon Kee ◽  
Mirko Cortese ◽  
Camila Metz Zumaran ◽  
Sergio Triana ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Critical Role ◽  
Intestinal Epithelial ◽  
Type Iii ◽  
Human Intestinal Epithelial Cells ◽  
Type Iii Interferon

scholarly journals Positive regulation of Type III secretion effectors and virulence by RyhB paralogs in Salmonella enterica serovar Enteritidis

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Binjie Chen ◽  
Xianchen Meng ◽  
Jie Ni ◽  
Mengping He ◽  
Yanfei Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Intestinal Epithelial Cells ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Intestinal Epithelial ◽  
Type Iii ◽  
Effector Gene ◽  
T3ss Effector

AbstractSmall non-coding RNA RyhB is a key regulator of iron homeostasis in bacteria by sensing iron availability in the environment. Although RyhB is known to influence bacterial virulence by interacting with iron metabolism related regulators, its interaction with virulence genes, especially the Type III secretion system (T3SS), has not been reported. Here, we demonstrate that two RyhB paralogs of Salmonella enterica serovar Enteritidis upregulate Type III secretion system (T3SS) effectors, and consequently affect Salmonella invasion into intestinal epithelial cells. Specifically, we found that RyhB-1 modulate Salmonella response to stress condition of iron deficiency and hypoxia, and stress in simulated intestinal environment (SIE). Under SIE culture conditions, both RyhB-1 and RyhB-2 are drastically induced and directly upregulate the expression of T3SS effector gene sipA by interacting with its 5′ untranslated region (5′ UTR) via an incomplete base-pairing mechanism. In addition, the RyhB paralogs upregulate the expression of T3SS effector gene sopE. By regulating the invasion-related genes, RyhBs in turn affect the ability of S. Enteritidis to adhere to and invade into intestinal epithelial cells. Our findings provide evidence that RyhBs function as critical virulence factors by directly regulating virulence-related gene expression. Thus, inhibition of RyhBs may be a potential strategy to attenuate Salmonella.

scholarly journals Cell Polarization and Epigenetic Status Shape the Heterogeneous Response to Type III Interferons in Intestinal Epithelial Cells

2017 ◽  
Vol 8 ◽  
Author(s):  
Sudeep Bhushal ◽  
Markus Wolfsmüller ◽  
Tharini A. Selvakumar ◽  
Lucas Kemper ◽  
Dagmar Wirth ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Cell Polarization ◽  
Intestinal Epithelial ◽  
Type Iii

scholarly journals Salmonella Type III Effector AvrA Stabilizes Cell Tight Junctions to Inhibit Inflammation in Intestinal Epithelial Cells

PLoS ONE ◽  
2008 ◽  
Vol 3 (6) ◽  
pp. e2369 ◽  
Author(s):  
Anne P. Liao ◽  
Elaine O. Petrof ◽  
Sumalatha Kuppireddi ◽  
Yun Zhao ◽  
Yinglin Xia ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junctions ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Type Iii Effector ◽  
Type Iii

scholarly journals Type III Interferon Restriction by Porcine Epidemic Diarrhea Virus and the Role of Viral Protein nsp1 in IRF1 Signaling

2017 ◽  
pp. JVI.01677-17 ◽  
Author(s):  
Qingzhan Zhang ◽  
Hanzhong Ke ◽  
Anthony Blikslager ◽  
Takashi Fujita ◽  
Dongwan Yoo
Keyword(s):  
Epithelial Cells ◽  
Porcine Epidemic Diarrhea Virus ◽  
Nuclear Translocation ◽  
Intestinal Epithelial Cells ◽  
Cell Model ◽  
Intestinal Epithelial ◽  
Diarrhea Virus ◽  
Type Iii ◽  
Porcine Epidemic Diarrhea ◽  
Type Iii Ifn

Type III interferons (IFN-λs) play a vital role to maintain the antiviral state of the mucosal epithelial surface in the gut, and in turn, enteric viruses may have evolved to evade the type III IFN responses during infection. To study of the possible immune evasion of porcine epidemic diarrhea virus (PEDV) from type III IFN response, a line of porcine intestinal epithelial cells was developed as a cell model for PEDV replication. IFN-λ1 and IFN-λ3 inhibited the PEDV replication, indicating the anti-PEDV activity of type III IFNs. Of the 21 PEDV proteins, nsp1, nsp3, nsp5, nsp8, nsp14, nsp15, nsp16, ORF3, E, M, and N were found to suppress the type III IFN activities, and the IRF1 signaling mediated the suppression. PEDV specifically inhibited IRF1 nuclear translocation. Peroxisome is the innate antiviral signaling platform for activation of IRF1-mediated IFN-λ production, and peroxisomes were found to decrease in number in PEDV-infected cells. PEDV nsp1 blocked the nuclear translocation of IRF1 and reduced the number of peroxisomes to suppress IRF1-mediated type III IFNs. Mutational studies showed the conserved residues of nsp1 were crucial for IRF1-mediated IFN-λ suppression. Our study for the first time provides the evidence that the porcine enteric virus PEDV downregulates and evades the IRF1-mediated type III IFN responses by reducing the peroxisomes.IMPORTANCEPorcine epidemic diarrhea virus (PEDV) is a highly contagious enteric coronavirus emerged in swine in the US and has caused severe economic losses. PEDV targets the intestinal epithelial cells in the gut, and intestinal epithelial cells selectively induce and respond to the production of type III interferons (IFNs). However, little is known about modulation of type III IFN response by PEDV in the intestinal epithelial cells. In this study, we established a porcine intestinal epithelial cell model for PEDV replication. We found that PEDV inhibited the IRF1-mediated type III IFN production by decreasing the peroxisomes in number in the porcine intestinal epithelial cells. We also demonstrated that the conserved residues in the PEDV nsp1 protein were crucial for IFN suppression. This study for the first time showed the PEDV evasion of type III IFN response in the intestinal epithelial cells. It provides valuable information on the host cell-virus interactions not only for PEDV but also other enteric viral infections in swine.

scholarly journals Rotavirus VP3 targets MAVS for degradation to inhibit type III interferon expression in intestinal epithelial cells

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Siyuan Ding ◽  
Shu Zhu ◽  
Lili Ren ◽  
Ningguo Feng ◽  
Yanhua Song ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Mammalian Species ◽  
Intestinal Epithelial ◽  
Structural Protein ◽  
Severe Diarrhea ◽  
Multiple Strategies ◽  
Type Iii Interferon ◽  
Proline Rich Region

Rotaviruses (RVs), a leading cause of severe diarrhea in young children and many mammalian species, have evolved multiple strategies to counteract the host innate immunity, specifically interferon (IFN) signaling through RV non-structural protein 1 (NSP1). However, whether RV structural components also subvert antiviral response remains under-studied. Here, we found that MAVS, critical for the host RNA sensing pathway upstream of IFN induction, is degraded by the RV RNA methyl- and guanylyl-transferase (VP3) in a host-range-restricted manner. Mechanistically, VP3 localizes to the mitochondria and mediates the phosphorylation of a previously unidentified SPLTSS motif within the MAVS proline-rich region, leading to its proteasomal degradation and blockade of IFN-λ production in RV-infected intestinal epithelial cells. Importantly, VP3 inhibition of MAVS activity contributes to enhanced RV replication and to viral pathogenesis in vivo. Collectively, our findings establish RV VP3 as a viral antagonist of MAVS function in mammals and uncover a novel pathogen-mediated inhibitory mechanism of MAVS signaling.

scholarly journals Inhibition of Type III Interferon Expression in Intestinal Epithelial Cells—A Strategy Used by Coxsackie B Virus to Evade the Host’s Innate Immune Response at the Primary Site of Infection?

2021 ◽  
Vol 9 (1) ◽  
pp. 105
Author(s):  
Virginia M. Stone ◽  
Emma E. Ringqvist ◽  
Pär G. Larsson ◽  
Erna Domsgen ◽  
Ulrika Holmlund ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Protein Translation ◽  
Primary Site ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Type I ◽  
Intestinal Epithelial ◽  
Type Iii

Increasing evidence highlights the importance of the antiviral activities of the type III interferons (IFNλs; IL-28A, IL-28B, IL29, and IFNλ4) in the intestine. However, many viruses have developed strategies to counteract these defense mechanisms by preventing the production of IFNs. Here we use infection models, a clinical virus isolate, and several molecular biology techniques to demonstrate that both type I and III IFNs induce an antiviral state and attenuate Coxsackievirus group B (CVB) replication in human intestinal epithelial cells (IECs). While treatment of IECs with a viral mimic (poly (I:C)) induced a robust expression of both type I and III IFNs, no such up-regulation was observed after CVB infection. The blunted IFN response was paralleled by a reduction in the abundance of proteins involved in the induction of interferon gene transcription, including TIR-domain-containing adapter-inducing interferon-β (TRIF), mitochondrial antiviral-signaling protein (MAVS), and the global protein translation initiator eukaryotic translation initiation factor 4G (eIF4G). Taken together, this study highlights a potent anti-Coxsackieviral effect of both type I and III IFNs in cells located at the primary site of infection. Furthermore, we show for the first time that the production of type I and III IFNs in IECs is blocked by CVBs. These findings suggest that CVBs evade the host immune response in order to successfully infect the intestine.

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