scholarly journals Antiviral Role of IFITM Proteins in Classical Swine Fever Virus Infection

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 126 ◽  
Author(s):  
Cheng Li ◽  
Hongqing Zheng ◽  
Yifan Wang ◽  
Wang Dong ◽  
Yaru Liu ◽  
...  
Keyword(s):  
Classical Swine Fever Virus ◽  
Mammalian Cells ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Late Endosomes ◽  
Early Endosomes ◽  
Infected Cells ◽  
The Relationship ◽  
Antiviral Role

The proteins IFITM1, IFITM2, and IFITM3 are host effectors against a broad range of RNA viruses whose roles in classical swine fever virus (CSFV) infection had not yet been reported. We investigated the effect of these proteins on CSFV replication in mammalian cells. The proteins were overexpressed and silenced using lentiviruses. Confocal microscopy was used to determine the distribution of these proteins in the cells, and immunofluorescence colocalization analysis was used to evaluate the relationship between IFITMs and the CSFV endosomal pathway, including early endosomes, late endosomes, and lysosomes. IFITM1, IFITM2, or IFITM3 overexpression significantly inhibited CSFV replication, whereas protein knockdown enhanced CSFV replication. In porcine alveolar macrophages (PAMs), IFITM1 was mainly located at the cell surface, whereas IFITM2 and IFITM3 were mainly located in the cytoplasm. Following CSFV infection, the distribution of IFITM1 changed. IFITM1, IFITM2, and IFITM3 colocalization with Lamp1, IFITM2 with Rab5 and Rab7, and IFITM3 with Rab7 were observed in CSFV-infected cells. Collectively, these results provide insights into the possible mechanisms associated with the anti-CSFV action of the IFITM family.

scholarly journals Antiviral Role of Serine Incorporator 5 (SERINC5) Proteins in Classical Swine Fever Virus Infection

2020 ◽  
Vol 11 ◽  
Author(s):  
Wenhui Li ◽  
Zilin Zhang ◽  
Liangliang Zhang ◽  
Hong Li ◽  
Shuangqi Fan ◽  
...  
Keyword(s):  
Virus Infection ◽  
Classical Swine Fever Virus ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Antiviral Role

scholarly journals Loss of Interferon Regulatory Factor 3 in Cells Infected with Classical Swine Fever Virus Involves the N-Terminal Protease, Npro

2005 ◽  
Vol 79 (11) ◽  
pp. 7239-7247 ◽  
Author(s):  
S. Anna La Rocca ◽  
Rebecca J. Herbert ◽  
Helen Crooke ◽  
Trevor W. Drew ◽  
Thomas E. Wileman ◽  
...  
Keyword(s):  
Classical Swine Fever Virus ◽  
Viral Protein ◽  
Sindbis Virus ◽  
Classical Swine Fever ◽  
Interferon Regulatory Factor ◽  
Fever Virus ◽  
Luciferase Reporter ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Infected Cells

ABSTRACT We show that cells infected with the pestivirus classical swine fever virus (CSFV) fail to produce alpha/beta interferon not only following treatment with double-stranded RNA but also after superinfection with a heterologous virus, the alphavirus Sindbis virus, a virus shown to normally induce interferon. We investigated whether the inhibition of interferon synthesis by CSFV involved a block in interferon regulatory factor 3 (IRF3) activity. Cells infected with CSFV exhibited a lack of translocation of green fluorescent protein-IRF3 to the nucleus; however, constitutive shuttling of IRF3 was not blocked, since it could still accumulate in the nucleus in the presence of leptomycin B. Interestingly subcellular fractionation analysis showed that IRF3 was lost from the cytoplasm of infected cells from 18 h postinfection onwards. Using IRF3 promoter-luciferase reporter constructs, we demonstrate that loss of IRF3 was due to an inhibition of transcription of the IRF3 gene in CSFV-infected cells. Further, we investigated which viral protein may be responsible for the inhibition of interferon and loss of IRF3. We used cell lines expressing the CSFV N-terminal protease (Npro) to show that this single viral protein, unique to pestiviruses, inhibited interferon production in response to Sindbis virus. In addition to being lost from CSFV-infected cells, IRF3 was lost from Npro-expressing cells. The results demonstrate a novel viral evasion of innate host defenses, where interferon synthesis is prevented by inhibiting transcription of IRF3 in CSFV-infected cells.

Role of birds in transmission of classical swine fever virus

2003 ◽  
Vol 50 (7) ◽  
pp. 357-359 ◽  
Author(s):  
V. Kaden ◽  
E. Lange ◽  
H. Steyer ◽  
W. Bruer ◽  
CH. Langner
Keyword(s):  
Classical Swine Fever Virus ◽  
Classical Swine Fever ◽  
Fever Virus

scholarly journals The E2 Glycoprotein of Classical Swine Fever Virus Is a Virulence Determinant in Swine

2005 ◽  
Vol 79 (6) ◽  
pp. 3787-3796 ◽  
Author(s):  
G. R. Risatti ◽  
M. V. Borca ◽  
G. F. Kutish ◽  
Z. Lu ◽  
L. G. Holinka ◽  
...  
Keyword(s):  
Classical Swine Fever Virus ◽  
Classical Swine Fever ◽  
Vaccine Virus ◽  
Fever Virus ◽  
Genetic Determinants ◽  
Highly Pathogenic ◽  
Virus Shedding ◽  
E2 Glycoprotein ◽  
Viral Virulence

ABSTRACT To identify genetic determinants of classical swine fever virus (CSFV) virulence and host range, chimeras of the highly pathogenic Brescia strain and the attenuated vaccine strain CS were constructed and evaluated for viral virulence in swine. Upon initial screening, only chimeras 138.8v and 337.14v, the only chimeras containing the E2 glycoprotein of CS, were attenuated in swine despite exhibiting unaltered growth characteristics in primary porcine macrophage cell cultures. Additional viral chimeras were constructed to confirm the role of E2 in virulence. Chimeric virus 319.1v, which contained only the CS E2 glycoprotein in the Brescia background, was markedly attenuated in pigs, exhibiting significantly decreased virus replication in tonsils, a transient viremia, limited generalization of infection, and decreased virus shedding. Chimeras encoding all Brescia structural proteins in a CS genetic background remained attenuated, indicating that additional mutations outside the structural region are important for CS vaccine virus attenuation. These results demonstrate that CS E2 alone is sufficient for attenuating Brescia, indicating a significant role for the CSFV E2 glycoprotein in swine virulence.

The Role of B Cells in the Immune Response to Pestivirus (Classical Swine Fever Virus)

2006 ◽  
Vol 135 (1) ◽  
pp. 32-41 ◽  
Author(s):  
P.J. Sánchez-Cordón ◽  
J.L. Romero-Trevejo ◽  
M. Pedrera ◽  
A.I. Raya ◽  
J.C. Gómez-Villamandos
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Classical Swine Fever Virus ◽  
Classical Swine Fever ◽  
Fever Virus

scholarly journals Classical swine fever virus NS5B protein suppresses the inhibitory effect of NS5A on viral translation by binding to NS5A

2012 ◽  
Vol 93 (5) ◽  
pp. 939-950 ◽  
Author(s):  
Chun Sheng ◽  
Jing Wang ◽  
Jing Xiao ◽  
Jun Xiao ◽  
Yan Chen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Classical Swine Fever Virus ◽  
Classical Swine Fever ◽  
Inhibitory Effect ◽  
Fever Virus ◽  
Viral Translation ◽  
Ns5a Protein ◽  
Gdd Motif ◽  
Ns5b Protein

In order to investigate molecular mechanisms of internal ribosome entry site (IRES)-mediated translation in classical swine fever virus (CSFV), an important pathogen of pigs, the expression level of NS3 was evaluated in the context of genomic RNAs and reporter RNA fragments. All data showed that the NS5A protein has an inhibitory effect on IRES-mediated translation and that NS5B proteins suppress the inhibitory effect of NS5A on viral translation, but CSFV NS5B GDD mutants do not. Furthermore, glutathione S-transferase pull-down assay and immunoprecipitation analysis, associated with deletion and alanine-scanning mutations, were performed. Results showed that NS5B interacts with NS5A and that the region aa 390–414, located in the C-terminal half of NS5A, is important for binding of NS5B to NS5A. Furthermore, amino acids K399, T401, E406 and L413 in the region were found to be essential for NS5A–NS5B interaction, virus rescue and infection. The above-mentioned region and four amino acids were observed to overlap with the site responsible for inhibition of IRES-mediated translation by the NS5A protein. We also found that aa 63–72, aa 637–653 and the GDD motif of NS5B were necessary for the interaction between NS5A and NS5B. These findings suggest that the repression activity of the NS5B protein toward the role of NS5A in translation might be achieved by NS5A–NS5B interaction, for which aa 390–414 of NS5A and aa 63–72, aa 637–653 and the GDD motif of NS5B are indispensable. This is important for understanding the role of NS5A–NS5B interaction in the virus life cycle.

scholarly journals Absence of autophagy promotes apoptosis by modulating the ROS-dependent RLR signaling pathway in classical swine fever virus-infected cells

Autophagy ◽  
2016 ◽  
Vol 12 (10) ◽  
pp. 1738-1758 ◽  
Author(s):  
Jingjing Pei ◽  
Jieru Deng ◽  
Zuodong Ye ◽  
Jiaying Wang ◽  
Hongchao Gou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Classical Swine Fever Virus ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Infected Cells

scholarly journals Mutation of Cysteine 171 of Pestivirus Erns RNase Prevents Homodimer Formation and Leads to Attenuation of Classical Swine Fever Virus

2009 ◽  
Vol 83 (10) ◽  
pp. 4823-4834 ◽  
Author(s):  
Birke Andrea Tews ◽  
Eva-Maria Schürmann ◽  
Gregor Meyers
Keyword(s):  
Classical Swine Fever Virus ◽  
Gel Electrophoresis ◽  
Bond Formation ◽  
Classical Swine Fever ◽  
Neutralizing Antibody ◽  
Fever Virus ◽  
Farm Animals ◽  
Protein Gel ◽  
Intermolecular Disulfide Bond ◽  
Infected Cells

ABSTRACT Pestiviruses represent important pathogens of farm animals that have evolved unique strategies and functions to stay within their host populations. Erns, a structural glycoprotein of pestiviruses, exhibits RNase activity and represents a virulence factor of the viruses. Erns forms disulfide linked homodimers that are found in virions and virus-infected cells. Mutation or deletion of cysteine 171, the residue engaged in intermolecular disulfide bond formation, results in loss of dimerization as tested in coprecipitation and native protein gel electrophoresis analyses. Nevertheless, stable virus mutants with changes affecting cysteine codon 171 could be recovered in tissue culture. These mutants grew almost as well as the parental viruses and exhibited an RNase-positive phenotype. Erns dimerization-negative mutants of classical swine fever virus were found to be attenuated in pigs even though the virus clearly replicated and induced a significant neutralizing antibody response in the animals.

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