CCL2 and CCL5 driven attraction of CD172a+ monocytic cells during an equine herpesvirus type 1 (EHV-1) infection in equine nasal mucosa and the impact of two migration inhibitors, rosiglitazone (RSG) and quinacrine (QC)

Zhao, Jing; Poelaert, Katrien C. K.; Cleemput, Jolien Van; Nauwynck, Hans

doi:10.1186/s13567-017-0419-4

Cited by 14 publications

(25 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The shedding of atypical porcine pestivirus in urine and saliva is in line with other publications [ 8 , 15 ], but our study is the first report where a commercial viral swab was used. When more details of the shedding of APPV are identified, saliva sampling could in the future be an easy and cost-effective way to screen large groups of pigs for the virus.…”

Section: Discussionsupporting

confidence: 92%

“…Interestingly, in the experimental infections described above, splay leg was induced in 0–40% of the piglets born from the sows inoculated with APPV [ 7 , 8 ]. This prevalence was an unusual observation of splay leg since the syndrome typically occurs only as sporadic cases [ 21 ], whereas congenital tremor commonly causes distinct, high-morbidity outbreaks [ 2 , 15 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Detection of atypical porcine pestivirus in Swedish piglets with congenital tremor type A-II

2020

View full text Add to dashboard Cite

Background: Congenital tremor (CT) type A-II is a neurological disorder characterized by tremor of the head and body of newborn piglets. The suggested causative agent of the disease is the recently found atypical porcine pestivirus (APPV). The virus has been detected in piglets suffering from congenital tremor in central Europe, South and North America and in China but no studies has so far been performed in the Nordic countries. The overarching goal of this study was to investigate if APPV is present in the brain tissue of Swedish piglets suffering from congenital tremor. From June 2017-June 2018, 15 piglets from four Swedish farms with ongoing outbreaks of congenital tremor and 13 piglets with splay leg originating from four different farms, were investigated for presence of APPV RNA in brain tissue. Matched healthy control piglets (n = 8) were also investigated. Two APPV-specific RT-qPCR methods targeting the NS3 and NS5B region, respectively, were used. A retrospective study was performed on material from Swedish piglets with congenital tremor sampled in 2004 (n = 11) and 2011/2012 (n = 3) using the described APPVspecific RT-qPCR methods. The total number of piglets with signs of CT in this study was 29. Results: Atypical porcine pestivirus-RNA was detected in 93% (27/29) of the piglets suffering from congenital tremor. All piglets with congenital tremor from 2004 (n = 11) and 2012 (n = 3) were PCR-positive with respect to APPV, whereas, all of the healthy controls (n = 11) were negative. The piglets with congenital tremor sampled 2017-2018 had an odds ratio of 91.8 (95% CI 3.9128 to 2153.7842, z = 2.807, P = 0.0050) to test positive for APPV by qRT-PCR compared to the healthy piglets (Fishers exact test p < 0.0001). These findings make it interesting to continue investigating APPV in the Swedish pig-population. Conclusion: This is the first description of atypical porcine pestivirus in piglets suffering from congenital tremor type A-II in Sweden and the Nordic countries. The virus has been present in the Swedish pig population since at least 2004.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Detection of atypical porcine pestivirus in Swedish piglets with congenital tremor type A-II

2020

View full text Add to dashboard Cite

show abstract

“…However, the abortigenic strains recruit fewer leukocytes into the URT, which enables the virus to replicate in the respiratory epithelium to promote viral shedding. Occupant immune cells become infected with abortigenic EHV1 in a less explosive and more controlled manner, followed by a silent transport in these “Trojan horses” to the pregnant uterus (Vandekerckhove et al, 2010 ; Laval et al, 2015 ; Zhao et al, 2017 ). In general, our findings support the speculation that the abortigenic variants may have a selective advantage over the neurovirulent variants for long-term maintenance within the equine population, by mastering the antiviral effect of IFN at the URT (Nugent et al, 2006 ; Goodman et al, 2007 ; Vandekerckhove et al, 2010 ; Laval et al, 2015 ; Zhao et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…Primary respiratory epithelial cells inoculated with the neurotropic Ab4 strain showed an up-regulation of mRNA expression of IFNα, which indicates the activation of the IFN response in the URT (Soboll Hussey et al, 2014 ). Intriguingly, recent studies of the URT demonstrated that chemokine expression varied between abortigenic and neurovirulent EHV1 strains in vivo and ex vivo (Holz et al, 2017 ; Zhao et al, 2017 ). A careful analysis of the early IFN response against EHV1 at the URT, and a comparison between abortigenic and neurovirulent variants may contribute to our understanding of the invasion kinetics of the two types of EHV1 in the URT.…”

Section: Introductionmentioning

confidence: 99%

Abortigenic but Not Neurotropic Equine Herpes Virus 1 Modulates the Interferon Antiviral Defense

Poelaert

Cleemput

Laval

et al. 2018

Front. Cell. Infect. Microbiol.

Self Cite

View full text Add to dashboard Cite

Equine herpesvirus 1 (EHV1) is considered as a major pathogen of Equidae, causing symptoms from mild respiratory disease to late-term abortion and neurological disorders. Different EHV1 strains circulating in the field have been characterized to be of abortigenic or neurovirulent phenotype. Both variants replicate in a plaque-wise manner in the epithelium of the upper respiratory tract (URT), where the abortigenic strains induce more prominent viral plaques, compared to the neurovirulent strains. Considering the differences in replication at the URT, we hypothesized that abortigenic strains may show an increased ability to modulate the type I IFN secretion/signaling pathway, compared to strains that display the neurovirulent phenotype. Here, we analyze IFN levels induced by abortigenic and neurovirulent EHV1 using primary respiratory epithelial cells (EREC) and respiratory mucosa ex vivo explants. Similar levels of IFNα (~70 U/ml) were detected in explants inoculated with both types of EHV1 strains from 48 to 72 hpi. Second, EREC and mucosa explants were treated with recombinant equine IFNα (rEqIFNα) or Ruxolitinib (Rux), an IFN signaling inhibitor, prior to and during inoculation with abortigenic or neurovirulent EHV1. Replication of both EHV1 variants was suppressed by rEqIFNα. Further, addition of Rux increased replication in a concentration-dependent manner, indicating an IFN-susceptibility for both variants. However, in two out of three horses, at a physiological concentration of 100 U/ml of rEqIFNα, an increase in abortigenic EHV1 replication was observed compared to 10 U/ml of rEqIFNα, which was not observed for the neurovirulent strains. Moreover, in the presence of Rux, the plaque size of the abortigenic variants remained unaltered, whereas the typically smaller viral plaques induced by the neurovirulent variants became larger. Overall, our results demonstrate the importance of IFNα in the control of EHV1 replication in the URT for both abortigenic and neurovirulent variants. In addition, our findings support the speculation that abortigenic variants of EHV1 may have developed anti-IFN mechanisms that appear to be absent or less pronounced in neurovirulent EHV1 strains.

show abstract

“…The process of cell-to-cell virus transfer from infected epithelial cells to PBMC is relatively simple. EHV-1 undergoes full replication cycles in the epithelium and the released infectious virus particles result in dendritic cell infection [ 81 , 82 , 83 ]. Since the mutant viruses can replicate to levels comparable to parental viruses ( Figure 2 A–C), it was not surprising to see no effect on virus spread between epithelial cells and PBMC.…”

Section: Discussionmentioning

confidence: 99%

Equine Herpesvirus Type 1 Modulates Cytokine and Chemokine Profiles of Mononuclear Cells for Efficient Dissemination to Target Organs

Pavulraj

Kamel

Stephanowitz

et al. 2020

Viruses

View full text Add to dashboard Cite

Equine herpesvirus type 1 (EHV-1) causes encephalomyelopathy and abortion, for which cell-associated viremia and subsequent virus transfer to and replication in endothelial cells (EC) are responsible and prerequisites. Viral and cellular molecules responsible for efficient cell-to-cell spread of EHV-1 between peripheral blood mononuclear cells (PBMC) and EC remain unclear. We have generated EHV-1 mutants lacking ORF1, ORF2, and ORF17 genes, either individually or in combination. Mutant viruses were analyzed for their replication properties in cultured equine dermal cells, PBMC infection efficiency, virus-induced changes in the PBMC proteome, and cytokine and chemokine expression profiles. ORF1, ORF2, and ORF17 are not essential for virus replication, but ORF17 deletion resulted in a significant reduction in plaque size. Deletion of ORF2 and ORF17 gene significantly reduced cell-to-cell virus transfer from virus-infected PBMC to EC. EHV-1 infection of PBMC resulted in upregulation of several pathways such as Ras signaling, oxidative phosphorylation, platelet activation and leukocyte transendothelial migration. In contrast, chemokine signaling, RNA degradation and apoptotic pathways were downregulated. Deletion of ORF1, ORF2 and ORF17 modulated chemokine signaling and MAPK pathways in infected PBMC, which may explain the impairment of virus spread between PBMC and EC. The proteomic results were further confirmed by chemokine assays, which showed that virus infection dramatically reduced the cytokine/chemokine release in infected PBMC. This study uncovers cellular proteins and pathways influenced by EHV-1 after PBMC infection and provide an important resource for EHV-1 pathogenesis. EHV-1-immunomodulatory genes could be potential targets for the development of live attenuated vaccines or therapeutics against virus infection.

show abstract

CCL2 and CCL5 driven attraction of CD172a+ monocytic cells during an equine herpesvirus type 1 (EHV-1) infection in equine nasal mucosa and the impact of two migration inhibitors, rosiglitazone (RSG) and quinacrine (QC)

Cited by 14 publications

References 42 publications

Detection of atypical porcine pestivirus in Swedish piglets with congenital tremor type A-II

Detection of atypical porcine pestivirus in Swedish piglets with congenital tremor type A-II

Abortigenic but Not Neurotropic Equine Herpes Virus 1 Modulates the Interferon Antiviral Defense

Equine Herpesvirus Type 1 Modulates Cytokine and Chemokine Profiles of Mononuclear Cells for Efficient Dissemination to Target Organs

Contact Info

Product

Resources

About