Porcine epidemic diarrhea virus infection induces NF-κB activation through the TLR2, TLR3 and TLR9 pathways in porcine intestinal epithelial cells

Cao, Liyan; Ge, Xianping; Gao, Yu; Ren, Yudong; Ren, Xiaofeng; Li, Guangxing

doi:10.1099/vir.0.000133

Cited by 81 publications

(86 citation statements)

References 44 publications

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“…Data showed that the inflammatory cytokines (such as IL-1β, IL-6, IL-8, CCL5, TNF-α, and MCP-1) were significantly down-regulated at 24 hpi when autophagy was inhibited in PEDV infected cells (Figure 6A,B), suggesting the potential involvement of autophagy in PEDV induced inflammation. It is well-known that the NF-κB signaling pathway plays a pivotal role in PEDV induced inflammatory response and Vero cells are interferon deficient [19,29]. Therefore, the influence of autophagy on the NF-κB pathway was determined under the deficient expression of Beclin1 and ATG5 at 24 h upon PEDV infection by immunoblotting analysis.…”

Section: Resultsmentioning

confidence: 99%

Porcine Epidemic Diarrhea Virus Induces Autophagy to Benefit Its Replication

Guo

Zhang

et al. 2017

Viruses

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The new porcine epidemic diarrhea (PED) has caused devastating economic losses to the swine industry worldwide. Despite extensive research on the relationship between autophagy and virus infection, the concrete role of autophagy in porcine epidemic diarrhea virus (PEDV) infection has not been reported. In this study, autophagy was demonstrated to be triggered by the effective replication of PEDV through transmission electron microscopy, confocal microscopy, and Western blot analysis. Moreover, autophagy was confirmed to benefit PEDV replication by using autophagy regulators and RNA interference. Furthermore, autophagy might be associated with the expression of inflammatory cytokines and have a positive feedback loop with the NF-κB signaling pathway during PEDV infection. This work is the first attempt to explore the complex interplay between autophagy and PEDV infection. Our findings might accelerate our understanding of the pathogenesis of PEDV infection and provide new insights into the development of effective therapeutic strategies.

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Section: Resultsmentioning

confidence: 99%

Porcine Epidemic Diarrhea Virus Induces Autophagy to Benefit Its Replication

Guo

Zhang

et al. 2017

Viruses

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“…While the ligand that activates TLR4 signaling following SARS-CoV infection has not yet been identified, our group has recently shown that TLR4 deficient mice are highly susceptible to SARS-CoV infection (Totura et al 2015). Other laboratories have demonstrated the importance of TLRs in the host immune response to porcine epidemic diarrhea virus (PEDV) (Cao et al 2015) and mouse hepatitis virus (Mazaleuskaya et al 2012), supporting a general requirement for TLR signaling in an effective immune response to coronavirus infection. TLR4 is classically known as the LPS receptor (Poltorak et al 1998), but it can also recognize host proteins that have altered expression under conditions of cell stress, such as heat shock proteins and proteins involved in the extracellular matrix (ECM) like fibrinogen, heparin sulfate, and hyaluronic acid (Okamura et al 2001; Smiley et al 2001; Cohen-Sfady et al 2005; Akbarshahi et al 2011).…”

Section: Discussionmentioning

confidence: 97%

Allelic Variation in the Toll-Like Receptor Adaptor ProteinTicam2Contributes to SARS-Coronavirus Pathogenesis in Mice

Gralinski

Menachery

Morgan

et al. 2017

G3 Genes|Genomes|Genetics

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Host genetic variation is known to contribute to differential pathogenesis following infection. Mouse models allow direct assessment of host genetic factors responsible for susceptibility to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). Based on an assessment of early stage lines from the Collaborative Cross mouse multi-parent population, we identified two lines showing highly divergent susceptibilities to SARS-CoV: the resistant CC003/Unc and the susceptible CC053/Unc. We generated 264 F2 mice between these strains, and infected them with SARS-CoV. Weight loss, pulmonary hemorrhage, and viral load were all highly correlated disease phenotypes. We identified a quantitative trait locus of major effect on chromosome 18 (27.1–58.6 Mb) which affected weight loss, viral titer and hemorrhage. Additionally, each of these three phenotypes had distinct quantitative trait loci [Chr 9 (weight loss), Chrs 7 and 12 (virus titer), and Chr 15 (hemorrhage)]. We identified Ticam2, an adaptor protein in the TLR signaling pathways, as a candidate driving differential disease at the Chr 18 locus. Ticam2−/− mice were highly susceptible to SARS-CoV infection, exhibiting increased weight loss and more pulmonary hemorrhage than control mice. These results indicate a critical role for Ticam2 in SARS-CoV disease, and highlight the importance of host genetic variation in disease responses.

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“…The sequences of specific siRNA oligonucleotides were as follows. TLR-sense: CCAGAUCUUUGAGCUCCAUTT; antisense: AU GGAGCUCAAAGAUCUG GTT; negative control-sense: UUCUCCGAACGUGUCACGUTT; antisense: ACGUG ACACGUUCGGAGAATT [55]. …”

Section: Methodsmentioning

confidence: 99%

Sodium butyrate improves porcine host defense peptide expression and relieves the inflammatory response upon toll-like receptor 2 activation and histone deacetylase inhibition in porcine kidney cells

et al. 2017

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Host defense peptides (HDPs) are an important component of the innate immune system and possess direct antimicrobial and immunomodulatory activities. Dietary regulation of HDPs synthesis has emerged as a novel non-antibiotic approach to combat pathogen infection. There are species- and tissue-dependent characteristics of the regulation and mechanism of HDPs. In this study, we investigated whether the histone deacetylase inhibitor (HDACi) sodium butyrate (NaB) could induce HDP expression and the mechanism underlying NaB-regulated HDP expression in PK-15 cells. Our results revealed that NaB augmented HDP expression in PK-15 cells, including porcine β-defensin 3 (pBD3), epididymis protein 2 splicing variant C (pEP2C), pBD128, pBD123, and pBD115, but no inflammatory response occurred. Inhibition of HDAC activity was not sufficient to induce the expression of pBD3 and pEP2C in comparisons of NaB and another HDACi, trichostatin A (TSA). Concomitantly, NF-κB activation was involved in the induction of HDP expression by NaB. MAPK pathway inhibition also prevented pBD3 and pEP2C induction by NaB. Furthermore, NaB could still promote pBD3 and pEP2C expression and inhibit IL-6 production in the presence of the toll-like receptor 2 (TLR2) ligand peptidoglycan. Moreover, TLR2 could be activated by both NaB and peptidoglycan, and blocking TLR2 expression suppressed HDP induction. Finally, we further showed that increased pBD3 could decrease cytokine interleukin-18 (IL-18) and increase porcine claudin 15 (pCLDN15) contents, suggesting an immunoregulatory function of pBD3. In conclusion, this work paves the way for using HDACi-NaB to induce porcine kidney defense peptides while limiting the deleterious risk of an inflammatory response.

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Porcine epidemic diarrhea virus infection induces NF-κB activation through the TLR2, TLR3 and TLR9 pathways in porcine intestinal epithelial cells

Cited by 81 publications

References 44 publications

Porcine Epidemic Diarrhea Virus Induces Autophagy to Benefit Its Replication

Porcine Epidemic Diarrhea Virus Induces Autophagy to Benefit Its Replication

Allelic Variation in the Toll-Like Receptor Adaptor ProteinTicam2Contributes to SARS-Coronavirus Pathogenesis in Mice

Sodium butyrate improves porcine host defense peptide expression and relieves the inflammatory response upon toll-like receptor 2 activation and histone deacetylase inhibition in porcine kidney cells

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