IL-22 suppresses the infection of porcine enteric coronaviruses and rotavirus by activating STAT3 signal pathway

Xue, Mei; Zhao, Jing; Li, Ying; Fu, Fang; Li, Lin; Ma, Yihui; Shi, Hongyan; Zhang, Jiaoer; Feng, Li; Liu, Pinghuang

doi:10.1016/j.antiviral.2017.03.006

Cited by 50 publications

(44 citation statements)

References 30 publications

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“…By demonstrating that IL-22 signaling is necessary and sufficient to drive epithelial claudin-2 upregulation in C. rodentium infection, these data link the previous observations and lead to the conclusion that IL-22-mediated claudin-2 expression occurs via a STAT-dependent process. Although IL-22 has not been previously recognized as a regulator of claudin-2 expression, other effects of IL-22-dependent epithelial STAT3 signaling, such as inhibition of enteric viral infection, might also reflect claudin-2 upregulation (Xue et al, 2017). Thus, claudin-2-mediated water efflux may be a widely used mechanism of innate defense.…”

Section: Discussionmentioning

confidence: 99%

IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance

Tsai

Zhang

et al. 2017

Cell Host & Microbe

209

200

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SUMMARY Diarrhea is a host response to enteric pathogens, but its impact on pathogenesis remains poorly defined. By infecting mice with the attaching and effacing bacteria Citrobacter rodentium, we defined the mechanisms and contributions of diarrhea and intestinal barrier loss to host defense. Increased permeability occurred within 2 days of infection and coincided with IL-22-dependent upregulation of the epithelial tight junction protein claudin-2. Permeability increases were limited to small molecules, as expected for the paracellular water and Na+ channel formed by claudin-2. Relative to wildtype, claudin-2-deficient mice experienced severe disease, including increased mucosal colonization by C. rodentium, prolonged pathogen shedding, exaggerated cytokine responses, and greater tissue injury. Conversely, transgenic claudin-2 overexpression reduced disease severity. Chemically-induced osmotic diarrhea reduced colitis severity and C. rodentium burden in claudin-2 deficient, but not transgenic, mice, demonstrating that claudin-2-mediated protection is the result of enhanced water efflux. Thus, IL-22-induced claudin-2 upregulation drives diarrhea and pathogen clearance.

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Section: Discussionmentioning

confidence: 99%

IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance

Tsai

Zhang

et al. 2017

Cell Host & Microbe

209

200

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“…Our data, shown that the expression level of IL-8 was up-regulated after PEDV infection of the host which may be beneficial for leukocyte accumulation during the inflammatory process triggered by PEDV infection. Xue et al [34] found that recombinant mature pIL-22 (mpIL-22) inhibited alpha coronavirus replication such as PEDV, transmissible gastroenteritis virus (TGEV) and porcine rotavirus (PoRV). In our study, the expression of IL-22 in porcine intestinal mucosa after PEDV infection was increased by 6.1 times compared with the mock infection.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis of small intestinal mucosa from porcine epidemic diarrhea virus infected piglets

Sun

Fahd

et al. 2019

Microbial Pathogenesis

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A B S T R A C TCaused by porcine epidemic diarrhea virus (PEDV), porcine epidemic diarrhea (PED) is an acute infectious disease which causes damage to the intestine including intestinal villus atrophy and shedding, leading to serious economic losses to the pig industry worldwide. In order to obtain detailed information about the pathogenesis and host immune response in a PEDV-infected host for first In vivo study we used high-throughput sequencing to analyze the gene expression differences of the small intestinal mucosa after infection with PEDV. Transcripts obtained were over 65,525,000 clean reads after reassembly were 22,605 genes detected, of which 22,248 were known genes and 371 new genes were predicted. Moreover, 3168 genes expression was up-regulated and 3876 genes down-regulated. (Gene Ontology) GO annotation and functional enrichment analysis indicated that all of the DEGs (differentially expressed genes) were annotated into biological process, cellular component and molecular function. Most of these unigenes are annotated in cellular processes, the cell and binding. KEGG analysis of the DEGs showed that a total of 7044 DEGs unigenes were annotated into 323 pathways classified into 6 main categories. Most of these unigenes are annotated were related to immune system response to the infectious diseases pathways. In addition, 20 DEGs were verified by quantitative real-time PCR. As the first, in vivo, RNAseq analysis of piglets and PEDV infection, our study provides knowledge about the transcriptomics of intestinal mucosa in PEDV-infected piglets, from which a complex molecular pathways and pathogenesis-related biological processes are involved in PEDV interaction with piglet intestinal mucosa.

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“…TGEV strain H87, derived from the virulent strain H16 (GenBank accession number FJ755618), was propagated in ST cells. A TGEV stock was prepared and titrated as previously described (56). For TGEV infection, ST cells were infected with TGEV H87 at the desired MOI or mock infected with DMEM.…”

Section: Methodsmentioning

confidence: 99%

The Coronavirus Transmissible Gastroenteritis Virus Evades the Type I Interferon Response through IRE1α-Mediated Manipulation of the MicroRNA miR-30a-5p/SOCS1/3 Axis

Wang

Xue

et al. 2018

J Virol

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In host innate immunity, type I interferons (IFN-I) are major antiviral molecules, and coronaviruses have evolved diverse strategies to counter the IFN-I response during infection. Transmissible gastroenteritis virus (TGEV), a member of the family, induces endoplasmic reticulum (ER) stress and significant IFN-I production after infection. However, how TGEV evades the IFN-I antiviral response despite the marked induction of endogenous IFN-I has remained unclear. Inositol-requiring enzyme 1 α (IRE1α), a highly conserved ER stress sensor with both kinase and RNase activities, is involved in the IFN response. In this study, IRE1α facilitated TGEV replication via downmodulating the host microRNA (miR) miR-30a-5p abundance. miR-30a-5p normally enhances IFN-I antiviral activity by directly targeting the negative regulators of Janus family kinase (JAK)-signal transducer and activator of transcription (STAT), the suppressor of cytokine signaling protein 1 (SOCS1), and SOCS3. Furthermore, TGEV infection increased SOCS1 and SOCS3 expression, which dampened the IFN-I antiviral response and facilitated TGEV replication. Importantly, compared with mock infection, TGEV infection resulted in decreased miR-30a-5p levels and significantly elevated SOCS1 and SOCS3 expression in the piglet ileum. Taken together, our data reveal a new strategy used by TGEV to escape the IFN-I response by engaging the IRE1α-miR-30a-5p/SOCS1/3 axis, thus improving our understanding of how TGEV escapes host innate immune defenses. Type I interferons (IFN-I) play essential roles in restricting viral infections. Coronavirus infection induces ER stress and the interferon response, which reflects different adaptive cellular processes. An understanding of how coronavirus-elicited ER stress is actively involved in viral replication and manipulates the host IFN-I response has remained elusive. Here, TGEV inhibited host miR-30a-5p via the ER stress sensor IRE1α, which led to the increased expression of negative regulators of JAK-STAT signaling cascades, namely, SOCS1 and SOCS3. Increased SOCS1 or SOCS3 expression impaired the IFN-I antiviral response, promoting TGEV replication. These findings enhance our understanding of the strategies used by coronaviruses to antagonize IFN-I innate immunity via IRE1α-mediated manipulation of the miR-30a-5p/SOCS axis, highlighting the crucial role of IRE1α in innate antiviral resistance and the potential of IRE1α as a novel target against coronavirus infection.

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IL-22 suppresses the infection of porcine enteric coronaviruses and rotavirus by activating STAT3 signal pathway

Cited by 50 publications

References 30 publications

IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance

IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance

Transcriptomic analysis of small intestinal mucosa from porcine epidemic diarrhea virus infected piglets

The Coronavirus Transmissible Gastroenteritis Virus Evades the Type I Interferon Response through IRE1α-Mediated Manipulation of the MicroRNA miR-30a-5p/SOCS1/3 Axis

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