scholarly journals Classical Swine Fever Virus Infection Induces Endoplasmic Reticulum Stress-Mediated Autophagy to Sustain Viral Replication in vivo and in vitro

2019 ◽  
Vol 10 ◽  
Author(s):  
Erpeng Zhu ◽  
Wenxian Chen ◽  
Yuwei Qin ◽  
Shengming Ma ◽  
Shuangqi Fan ◽  
...  

2006 ◽  
Vol 37 (1) ◽  
pp. 155-168 ◽  
Author(s):  
Henriette Rau ◽  
Hilde Revets ◽  
Carole Balmelli ◽  
Kenneth C. McCullough ◽  
Artur Summerfield




2012 ◽  
Vol 9 (1) ◽  
Author(s):  
Li-Jun Chen ◽  
Xiao-Ying Dong ◽  
Ming-Qiu Zhao ◽  
Hai-Yan Shen ◽  
Jia-Ying Wang ◽  
...  


2004 ◽  
Vol 78 (16) ◽  
pp. 8812-8823 ◽  
Author(s):  
H. G. P. van Gennip ◽  
A. C. Vlot ◽  
M. M. Hulst ◽  
A. J. de Smit ◽  
R. J. M. Moormann

ABSTRACT Two related classical swine fever virus (CSFV) strain Brescia clones were isolated from blood samples from an infected pig. Virus C1.1.1 is a cell-adapted avirulent variant, whereas CoBrB is a virulent variant. Sequence analysis revealed 29 nucleic acid mutations in C1.1.1, resulting in 9 amino acid substitutions compared to the sequence of CoBrB 476R. Using reverse genetics, parts of the genomes of these viruses, which contain differences that lead to amino acid changes, were exchanged. Animal experiments with chimeric viruses derived from C1.1.1 and CoBrB 476R showed that a combination of amino acid changes in the structural and nonstructural regions reduced the virulence of CSFV in pigs. Moreover, the presence of a Leu at position 710 in structural envelope protein E2 seemed to be an important factor in the virulence of the virus. Changing the Leu at position 710 in the CoBrB 476S variant into a His residue did not affect virulence. However, the 710His in the C1.1.1/CoBrB virus, together with adaptive mutations 276R, 476R, and 477I in Erns, resulted in reduced virulence in pigs. These results indicated that mutations in Erns and E2 alone do not determine virulence in pigs. The results of in vitro experiments suggested that a high affinity for heparan sulfate of C1.1.1 Erns may reduce the spread of the C1.1.1/CoBrB virus in pigs and together with the altered surface structure of E2 caused by the 710L→H mutation may result in a less efficient infection of specific target cells in pigs. Both these features contributed to the attenuation of the C1.1.1/CoBrB virus in vivo.



2005 ◽  
Vol 40 (5) ◽  
pp. 415-421
Author(s):  
E Schuurmann ◽  
G Flogel-Niesmann ◽  
V Monnig ◽  
D Rath


2015 ◽  
Vol 160 (12) ◽  
pp. 3121-3125 ◽  
Author(s):  
Katja V. Goller ◽  
Carolin Dräger ◽  
Dirk Höper ◽  
Martin Beer ◽  
Sandra Blome


2012 ◽  
Vol 86 (16) ◽  
pp. 8602-8613 ◽  
Author(s):  
Tomokazu Tamura ◽  
Yoshihiro Sakoda ◽  
Fumi Yoshino ◽  
Takushi Nomura ◽  
Naoki Yamamoto ◽  
...  

Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious disease of pigs. There are numerous CSFV strains that differ in virulence, resulting in clinical disease with different degrees of severity. Low-virulent and moderately virulent isolates cause a mild and often chronic disease, while highly virulent isolates cause an acute and mostly lethal hemorrhagic fever. The live attenuated vaccine strain GPE−was produced by multiple passages of the virulent ALD strain in cells of swine, bovine, and guinea pig origin. With the aim of identifying the determinants responsible for the attenuation, the GPE−vaccine virus was readapted to pigs by serial passages of infected tonsil homogenates until prolonged viremia and typical signs of CSF were observed. The GPE−/P-11 virus isolated from the tonsils after the 11th passagein vivohad acquired 3 amino acid substitutions in E2 (T830A) and NS4B (V2475A and A2563V) compared with the virus before passages. Experimental infection of pigs with the mutants reconstructed by reverse genetics confirmed that these amino acid substitutions were responsible for the acquisition of pathogenicity. Studiesin vitroindicated that the substitution in E2 influenced virus spreading and that the changes in NS4B enhanced the viral RNA replication. In conclusion, the present study identified residues in E2 and NS4B of CSFV that can act synergistically to influence virus replication efficiencyin vitroand pathogenicity in pigs.



2018 ◽  
Author(s):  
Haisi Dong ◽  
Dongmei Lv ◽  
Ang Su ◽  
Lerong Ma ◽  
Jianwei Dong ◽  
...  

AbstractClassical swine fever (CSF) is a highly contagious swine disease found worldwide that has caused devastating economic losses. However, there are few efficacious mAbs against the CSF virus (CSFV) that can be used for treatment because most mAbs against CSFV are derived from mouse hybridoma cells and these murine mAbs have disadvantages of inefficient effector functions elicitations and high immunogenicity in vivo. Accordingly, we characterized whole-porcine anti-CSFV neutralizing mAbs (NAbs) isolated directly from single B cells sorted from a CSFV-vaccinated pig using the fluoresceinated conserved linear neutralizing epitope of the CSFV E2 protein and fluorophore conjugated goat anti-pig IgG. Immunoglobulin (Ig) genes were isolated via nested PCR, and two porcine mAbs termed HK24 and HK44 were produced. We determined that these mAbs can bind to E2 protein and recognize sites within this major antigenic epitope. In addition, we found that mAbs HK24 and HK44 exhibit potent neutralizing activity against CSFV, and they can protect PK-15 cells from infections in vitro with potent IC50 values of 9.3 μg/ml and 0.62 μg/ml, respectively. Notably, we demonstrated that these two mAbs can be used as novel reagents for detecting virus infection. These data suggest that our results not only provide a method for efficiently obtaining mAbs against CSFV but also offer promising mAb candidates for development of antibody-based diagnostic and antiviral agents.ImportanceNeutralizing monoclonal antibodies (NAbs) can prevent and may slow the spread of virus infection. The discovery of NAbs that recognize classical swine fever virus (CSFV) necessitates new technologies because the NAbs produced by immunization and hybridoma technology could not be transferred to in vivo research. Multiple full-length human therapeutic antibodies have been produced via single-cell polymerase chain reactions but whole-porcine NAbs for CSFV have not been generated. In this study, two whole-porcine mAbs, named HK24 and HK44, were isolated from epitope-specific single B cells. We demonstrate that these two mAbs have potent neutralizing activity against CSFV and can protect cells against viral infection. Therefore, they may facilitate the development of vaccines or antiviral drugs that offer the advantages of stability and low immunogenicity.



2018 ◽  
Author(s):  
Zicong Xie ◽  
Daxin Pang ◽  
Hongming Yuan ◽  
Huping Jiao ◽  
Chao Lu ◽  
...  

AbstractClassical swine fever (CSF) caused by classical swine fever virus (CSFV) is among the most detrimental diseases, and leads to significant economic losses in the swine industry. Despite efforts by many government authorities try to stamp out the disease from national pig populations, the disease remains widespread. Here, antiviral small hairpin RNAs (shRNAs) were selected and then inserted at the porcine ROSA26 (pROSA26) locus via a CRISPR/Cas9-mediated knock-in strategy. Finally, anti-CSFV transgenic (TG) pigs were produced by somatic nuclear transfer (SCNT). Importantly, in vitro and in vivo viral challenge assays demonstrated that these TG pigs could effectively limit the growth of CSFV and reduced CSFV-associated clinical signs and mortality, and the disease resistance was stably transmitted to F1-generation. The use of these TG pigs can improve the well-being of livestock and substantially reduce virus-related economic losses. Additionally, this antiviral approach may provide a reference for future antiviral research.Author summaryClassical swine fever (CSF), caused by classical swine fever virus (CSFV), and is a highly contagious, often fatal porcine disease with significant economic losses. Due to its economic importance to the pig industry, the biology and pathogenesis of CSFV have been investigated extensively. Despite efforts by many government authorities to stamp out the disease from national pig populations, the disease remains widespread in some regions and seems to be waiting for the reintroduction and the next round of disease outbreaks. These highlight the necessity and urgency of developing more effective approaches to eradicate the challenging CSFV. In this study, we successfully produced anti-CSFV transgenic pigs and confirmed that these transgenic pigs could effectively limit the growth of CSFV in vivo and in vitro and that the disease resistance traits in the TG founders can be stably transmitted to their F1-generation offspring. This study suggests that these TG pigs can improve the well-being of livestock and contribute to offer potential benefits over commercial vaccination. The use of these TG pigs can improve the well-being of livestock and substantially reduce CSFV-related economic losses.



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