Transmissible gastroenteritis virus and porcine epidemic diarrhoea virus infection induces dramatic changes in the tight junctions and microfilaments of polarized IPEC-J2 cells

Zhao, Shanshan; Gao, Junkai; Zhu, Liqi; Yang, Qian

doi:10.1016/j.virusres.2014.08.014

Cited by 75 publications

(71 citation statements)

References 35 publications

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“…PEDV, transmissible gastroenteritis virus (TGEV) and porcine rotavirus are major swine pathogens that cause viral gastroenteritis, and the target of these viruses is the intestinal epithelium (Liu et al, 2010;Zhao et al, 2014). Therefore, IECs are optimal for studying the pathogenic mechanisms of these viruses, owing to their strong similarities with primary intestinal epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

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

Cao

Gao

et al. 2015

Journal of General Virology

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Porcine epidemic diarrhea virus (PEDV) is a coronavirus that induces persistent diarrhoea in swine, resulting in severe economic losses in swine-producing countries. Insights into the interplay between PEDV infection and the innate immune system are necessary for understanding the associated mechanism of pathogenesis. The transcription factor NF-kB plays an important role in regulating host immune responses. Here, we elucidated for the first time to our knowledge the potential mechanism of PEDV-mediated NF-kB activation in porcine small intestinal epithelial cells (IECs). During PEDV infection, NF-kB p65 was found to translocate from the cytoplasm to the nucleus, and PEDV-dependent NF-kB activity was associated with viral dose and active replication. Using small interfering RNAs to screen different mRNA components of the Toll-like receptor (TLR) or RIG-I-like receptor signalling pathways, we demonstrated that TLR2, TLR3 and TLR9 contribute to NF-kB activation in response to PEDV infection, but not RIG-I. By screening PEDV structural proteins for their ability to induce NF-kB activities, we found that PEDV nucleocapsid protein (N) could activate NF-kB and that the central region of N was essential for NF-kB activation. Furthermore, TLR2 was involved in PEDV N-induced NF-kB activation in IECs. Collectively, these findings provide new avenues of investigation into the molecular mechanisms of NF-kB activation induced by PEDV infection.

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Section: Introductionmentioning

confidence: 99%

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

Cao

Gao

et al. 2015

Journal of General Virology

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“…In addition to occludin, the tight junction protein claudin-1 is tightly related to the infection of dengue virus, HCV, West Nile virus, and others (25)(26)(27)(28). During PEDV infection, it has been demonstrated that structural destruction and disorganization of tight junctions are observed (12,29). However, the role of tight junctions in PEDV infection has not yet been defined.…”

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confidence: 99%

Tight Junction Protein Occludin Is a Porcine Epidemic Diarrhea Virus Entry Factor

Luo

Guo

Zhang

et al. 2017

J Virol

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Porcine epidemic diarrhea virus (PEDV), the causative agent of porcine epidemic diarrhea, has caused huge economic losses in pig-producing countries. Although PEDV was long believed to replicate in the intestinal epithelium by using aminopeptidase N as a receptor, the mechanisms of PEDV infection are not fully characterized. In this study, we found that PEDV infection of epithelial cells results in disruption of the tight junctional distribution of occludin to its intracellular location. Overexpression of occludin in target cells makes them more susceptible to PEDV infection, whereas ablation of occludin expression by use of small interfering RNA (siRNA) in target cells significantly reduces their susceptibility to virus infection. However, the results observed with occludin siRNA indicate that occludin is not required for virus attachment. We conclude that occludin plays an essential role in PEDV infection at the postbinding stages. Furthermore, we observed that macropinocytosis inhibitors blocked occludin internalization and virus entry, indicating that virus entry and occludin internalization are closely coupled. However, the macropinocytosis inhibitors could not impede virus replication once the virus had entered host cells. This suggests that occludin internalization by macropinocytosis or a macropinocytosis-like process is involved in the virus entry events. Immunofluorescence confocal microscopy showed that PEDV was trapped at cellular junctional regions upon macropinocytosis inhibitor treatment, indicating that occludin may serve as a scaffold in the vicinity of virus entry. Collectively, these data show that occludin plays an essential role in PEDV infection during late entry events. Our observation may provide novel insights into PEDV infection and related pathogenesis.IMPORTANCE Tight junctions are highly specialized membrane domains whose main function is to attach adjacent cells to each other, thereby forming intercellular seals. Here we investigate, for the first time, the role of the tight junction protein occludin in PEDV infection. We observed that PEDV infection induced the internalization of occludin. By using genetic modification methods, we demonstrate that occludin plays an essential role in PEDV infection. Moreover, PEDV entry and occludin internalization seem to be closely coupled. Our findings reveal a new mechanism of PEDV infection.KEYWORDS PEDV, occludin, tight junction C oronaviruses are a group of positive-strand RNA viruses belonging to the family Coronaviridae in the order Nidovirales. They are broadly distributed among mammalian and avian species, and they cause acute and persistent infections. In most cases, coronaviruses are generally associated with significant respiratory and/or intestinal tract diseases (1, 2). Porcine epidemic diarrhea virus (PEDV) has been identified as the etiologic agent of porcine epidemic diarrhea (PED), and it causes diarrhea, vomiting, and dehydration in infected swine (3, 4). Outbreaks of PED have occurred frequently in

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“…After infection of polarized porcine intestinal epithelial cells (IPEC-J2), TGEV and PEDV induced MAPK activation to affect cell microfilaments and alter epithelial barrier integrity (Zhao et al, 2014). In both TGEV and PEDV infection, ERK activation is required for efficient virus replication.…”

Section: Host Cell Pathways Involved In Pathogenesismentioning

confidence: 99%

Virulence factors in porcine coronaviruses and vaccine design

et al. 2016

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Porcine enteric coronaviruses (CoVs) cause severe disease in the porcine herds worldwide, leading to important economic losses. Despite the knowledge of these viruses since the 1970’s, vaccination strategies have not been implemented, leading to continuous re-emergence of novel virulent strains. Live attenuated vaccines historically have been the most efficient. We consider that the new trend is the development of recombinant vaccines by using reverse genetics systems to engineer attenuated viruses, which could be used as effective and safe modified live vaccine candidates. To this end, host cell signaling pathways influencing porcine CoV virulence should be identified. Similarly, the identity of viral proteins involved in the modulation of host cell pathways influencing CoV pathogenesis should be analyzed. With this information, and using reverse genetics systems, it is possible to design viruses with modifications in the viral proteins acting as virulence factors, which may lead to attenuated viruses and, therefore, vaccine candidates. In addition, novel antiviral drugs may be developed once the host cell pathways and the molecular mechanism affecting porcine CoV replication and virulence are known. This review is focused in the host cell responses to enteric porcine CoV infection and the viral proteins involved in pathogenesis.

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Transmissible gastroenteritis virus and porcine epidemic diarrhoea virus infection induces dramatic changes in the tight junctions and microfilaments of polarized IPEC-J2 cells

Cited by 75 publications

References 35 publications

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

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

Tight Junction Protein Occludin Is a Porcine Epidemic Diarrhea Virus Entry Factor

Virulence factors in porcine coronaviruses and vaccine design

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