Short communication: antiviral activity of porcine IFN-λ3 against porcine epidemic diarrhea virus in vitro

Shen, Huiyong; Zhang, Chunhong; Guo, Pengju; Liu, Zhicheng; Sun, Mingfei; Sun, Junying; Li, Linlin; Dong, Jiawen; Zhang, Jianfeng

doi:10.1007/s11262-016-1374-2

Cited by 16 publications

(14 citation statements)

References 26 publications

(7 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reovirus replicates in both epithelial and nonepithelial cells (43), and thus, type I and type III IFNs cooperatively control reovirus infection such that type III IFNs restrict infection in epithelial cells, whereas type I IFNs exert antiviral activity on nonepithelial cells (14). Recombinant swine type III IFNs have been shown to restrict PEDV infection in both Vero and IPEC-J2 cells (44,45). We have also shown that type III IFNs restrict PEDV infection in a dose-dependent manner (Fig.…”

Section: Discussionmentioning

confidence: 59%

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

Zhang

Blikslager

et al. 2018

J Virol

122

161

View full text Add to dashboard Cite

Type III interferons (IFNs) play a vital role in maintaining 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 the possible immune evasion of the type III IFN response by porcine epidemic diarrhea virus (PEDV), a line of porcine intestinal epithelial cells was developed as a cell model for PEDV replication. IFN-λ1 and IFN-λ3 inhibited PEDV replication, indicating the anti-PEDV activity of type III IFNs. Of the 21 PEDV proteins, nsp1, nsp3, nsp5, nsp8, nsp14, nsp15, nsp16, open reading frame 3 (ORF3), E, M, and N were found to suppress type III IFN activities, and IRF1 (interferon regulatory factor 1) signaling mediated the suppression. PEDV specifically inhibited IRF1 nuclear translocation. The peroxisome is the innate antiviral signaling platform for the activation of IRF1-mediated IFN-λ production, and the numbers of peroxisomes were found to be decreased 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 that the conserved residues of nsp1 were crucial for IRF1-mediated IFN-λ suppression. Our study for the first time provides evidence that the porcine enteric virus PEDV downregulates and evades IRF1-mediated type III IFN responses by reducing the number of peroxisomes. Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric coronavirus that emerged in swine in the United States and has caused severe economic losses. PEDV targets 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 the modulation of the type III IFN response by PEDV in intestinal epithelial cells. In this study, we established a porcine intestinal epithelial cell model for PEDV replication. We found that PEDV inhibited IRF1-mediated type III IFN production by decreasing the number of peroxisomes in 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 shows PEDV evasion of the type III IFN response in intestinal epithelial cells, and it provides valuable information on host cell-virus interactions not only for PEDV but also for other enteric viral infections in swine.

show abstract

Section: Discussionmentioning

confidence: 59%

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

Zhang

Blikslager

et al. 2018

J Virol

122

161

View full text Add to dashboard Cite

show abstract

“…The total RNA was extracted and subjected to the real-time RT-PCR analysis to evaluate the host immune responses induced by PEDV on IPEC-J2 cells. The type III interferon has been reported to play a vital role in maintaining the antiviral state of the mucosal epithelial cell surface in the gut and resist PEDV infection Shen et al, 2016;Zhang et al, 2018). Therefore, the IFN-λ1 and IFN-λ3 were selected to monitor antiviral responses and results showed that their expression levels were significantly upregulated and reached their peaks at 36 hpi and dropped to the normal level thereafter (Fig.…”

Section: Samples At Immune Active Stages Were Selected For Circrna Sementioning

confidence: 99%

Profile analysis of circRNAs induced by porcine endemic diarrhea virus infection in porcine intestinal epithelial cells

et al. 2019

View full text Add to dashboard Cite

The circRNA is a newly defined noncoding RNA and characterized by its unique splicing reactions to form circles. However, the function of circRNAs during viral infection remains largely unknown. In this study, the circRNA expression profile during porcine endemic diarrhea virus (PEDV) infection in IPEC-J2 cell line was investigated using the next-generation sequencing technology. A total of 26670 circRNA candidates were identified. The functional annotation analysis revealed that the parent genes of differentially expressed circRNAs might be associated with host response to PEDV infection. Further analysis verified the existence of eight selected circRNAs and confirmed that PEDV infection alerted the expression patterns of circRNAs and their linear parent genes in IPEC-J2 cell line. The circRNA-miRNA interaction network was also constructed to elucidate their potential targets. Our results provided not only the first large-scale profile analysis of circRNAs associated with PEDV infection but also a novel direction to elucidate host-PEDV interactions.

show abstract

“…Additionally, extracellular ISG15 has several immunomodulatory activities such as the induction of natural killer cell proliferation and the stimulation of IFNproduction, triggering a type II IFN response (Bogunovic et al, 2012). ISG15 has also been linked to effective antiviral type III IFN responses (Shen et al, 2016;Murakawa et al, 2017;Fan et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement

Langley

Goodwin

Dzimianski

et al. 2019

Acta Cryst Sect D Struct Biol

View full text Add to dashboard Cite

Bats have long been observed to be the hosts and the origin of numerous human diseases. Bats, like all mammals, rely on a number of innate immune mechanisms to combat invading pathogens, including the interferon type I, II and III responses. Ubiquitin-like interferon-stimulated gene product 15 (ISG15) is a key modulator of these interferon responses. Within these pathways, ISG15 can serve to stabilize host proteins modulating innate immune responses and act as a cytokine. Post-translational modifications of viral proteins introduced by ISG15 have also been observed to directly affect the function of numerous viral proteins. Unlike ubiquitin, which is virtually identical across all animals, comparison of ISG15s across species reveals that they are relatively divergent, with sequence identity dropping to as low as $58% among mammals. In addition to serving as an obstacle to the zoonotic transmission of influenza, these ISG15 species-species differences have also long been shown to have an impact on the function of viral deISGylases. Recently, the structure of the first nonhuman ISG15, originating from mouse, suggested that the structures of human ISG15 may not be reflective of other species. Here, the structure of ISG15 from the bat species Myotis davidii solved to 1.37 Å resolution is reported. Comparison of this ISG15 structure with those from human and mouse not only underscores the structural impact of ISG15 species-species differences, but also highlights a conserved hydrophobic motif formed between the two domains of ISG15. Using the papain-like deISGylase from Severe acute respiratory syndrome coronavirus as a probe, the biochemical importance of this motif in ISG15-protein engagements was illuminated.

show abstract

Short communication: antiviral activity of porcine IFN-λ3 against porcine epidemic diarrhea virus in vitro

Cited by 16 publications

References 26 publications

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

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

Profile analysis of circRNAs induced by porcine endemic diarrhea virus infection in porcine intestinal epithelial cells

Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement

Contact Info

Product

Resources

About