scholarly journals The DDX23 Negatively Regulates Translation and Replication of Foot-and-Mouth Disease Virus and Is Degraded by 3C Proteinase

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1348
Author(s):  
Sahibzada Waheed Abdullah ◽  
Shichong Han ◽  
Jin’en Wu ◽  
Yun Zhang ◽  
Manyuan Bai ◽  
...  
Keyword(s):  
Disease Virus ◽  
Small Interfering Rna ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Dependent Manner ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Rna Knockdown ◽  
Interfering Rna ◽  
Fmdv Replication

DEAD-box helicase 23 (DDX23) is a host nuclear helicase, which is a part of the spliceosomal complex and involved in pre-mRNA splicing. To investigate whether DDX23, an internal ribosomal entry sites transacting factor (ITAF) affects foot-and-mouth disease virus (FMDV) replication and translation through internal ribosome entry site (IRES)-dependent manner. For this, we utilized a pull-down assay, Western blotting, quantitative real-time PCR, confocal microscopy, overexpression and small interfering RNA knockdown, as well as the median tissue culture infective dose. Our findings showed that FMDV infection inhibited DDX23 expression and the overexpression of DDX23 reduced viral replication, however, CRISPR Cas9 knockout/small interfering RNA knockdown increased FMDV replication. FMDV IRES domain III and IV interacted with DDX23, whereas DDX23 interacted with FMDV 3C proteinase and significantly degraded. The enzymatic activity of FMDV 3C proteinase degraded DDX23, whereas FMDV degraded DDX23 via the lysosomal pathway. Additionally, IRES-driven translation was suppressed in DDX23-overexpressing cells, and was enhanced in DDX23 knocked down. Collectively, our results demonstrated that DDX23 negatively affects FMDV IRES-dependent translation, which could be a useful target for the design of antiviral drugs.

scholarly journals Lithium chloride inhibits early stages of foot-and-mouth disease virus (FMDV) replication in vitro

2017 ◽  
Vol 89 (11) ◽  
pp. 2041-2046 ◽  
Author(s):  
Fu-Rong Zhao ◽  
Yin-Li Xie ◽  
Ze-Zhong Liu ◽  
Jun-Jun Shao ◽  
Shi-Fang Li ◽  
...  
Keyword(s):  
Disease Virus ◽  
Lithium Chloride ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Early Stages ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Fmdv Replication

scholarly journals Basal Level p53 Suppresses Antiviral Immunity against Foot-and-Mouth Disease Virus

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 727
Author(s):  
Zhang ◽  
Chen ◽  
Liu ◽  
Qi ◽  
Gao ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Disease Virus ◽  
Knockout Mice ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Clear Cut ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Immune Related Genes ◽  
Fmdv Replication

Tumor suppressor protein p53 (p53) is a master transcription factor that plays key roles in cell cycle arrest, apoptosis, senescence, and metabolism, as well as regulation of innate immunity during virus infection. In order to facilitate their replication and spreading, viruses have evolved to manipulate p53 function through different strategies, with some requiring active p53 while others demand reduction/inhibition of p53 activity. However, there are no clear-cut reports about the roles of p53 during the infection of foot-and-mouth disease virus (FMDV), the causative agent of a highly contagious foot-and-mouth disease (FMD) of cloven-hoofed animals. Here we showed that p53 level was dynamically regulated during FMDV infection, being degraded at the early infection stage but recovered to the basal level at the late stage. Cells depleted of p53 showed inhibited FMDV replication and enhanced expression of the immune-related genes, whereas overexpression of p53 didn’t affect the viral replication. Viral challenge assay with p53 knockout mice obtained similar results, with viral load decreased, histopathological changes alleviated, and lifespan extended in the p53 knockout mice. Together, these data demonstrate that basal level p53 is required for efficient FMDV replication by suppressing the innate immunity.

scholarly journals The Kinase STK3 Interacts with the Viral Structural Protein VP1 and Inhibits Foot-and-Mouth Disease Virus Replication

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Huisheng Liu ◽  
Qiao Xue ◽  
Qiaoying Zeng ◽  
Zixiang Zhu ◽  
Haixue Zheng
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Host Cells ◽  
Cell Protein ◽  
Structural Protein ◽  
New Information ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Fmdv Replication

Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects domestic and wild cloven-hoofed animals. The structural protein VP1 plays an important role in FMDV pathogenesis. However, the interacting partners of VP1 in host cells and the effects of these interactions in FMDV replication remain incompletely elucidated. Here, we identified a porcine cell protein, serine/threonine kinase 3 (STK3), which interacts with FMDV VP1 using the yeast two-hybrid system. The VP1-STK3 interaction was further confirmed by coimmunoprecipitation experiments in human embryonic kidney 293T and porcine kidney 15 (PK-15) cells. The carboxyl-terminal region (amino acids 180–214) of VP1 was essential for its interaction with STK3. The effects of overexpression and underexpressing of STK3 in PK-15 cells were assessed, and the results indicated that STK3 significantly inhibited FMDV replication. Our data expand the role of STK3 during viral infection, provide new information regarding the host cell kinases that are involved in viral replication, and identify potential targets for future antiviral strategies.

scholarly journals Assembly and characterization of foot-and-mouth disease virus empty capsid particles expressed within mammalian cells

2013 ◽  
Vol 94 (8) ◽  
pp. 1769-1779 ◽  
Author(s):  
Maria Gullberg ◽  
Bartosz Muszynski ◽  
Lindsey J. Organtini ◽  
Robert E. Ashley ◽  
Susan L. Hafenstein ◽  
...  
Keyword(s):  
Disease Virus ◽  
Mammalian Cells ◽  
Expression System ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Capsid Proteins ◽  
Dependent Manner ◽  
Empty Capsid ◽  
Mouth Disease Virus ◽  
Foot And Mouth

The foot-and-mouth disease virus (FMDV) structural protein precursor, P1-2A, is cleaved by the virus-encoded 3C protease (3Cpro) into the capsid proteins VP0, VP1 and VP3 (and 2A). In some systems, it is difficult to produce large amounts of these processed capsid proteins since 3Cpro can be toxic for cells. The expression level of 3Cpro activity has now been reduced relative to the P1-2A, and the effect on the yield of processed capsid proteins and their assembly into empty capsid particles within mammalian cells has been determined. Using a vaccinia-virus-based transient expression system, P1-2A (from serotypes O and A) and 3Cpro were expressed from monocistronic cDNA cassettes as P1-2A-3C, or from dicistronic cassettes with the 3Cpro expression dependent on a mutant FMDV internal ribosome entry site (IRES) (designated P1-2A-mIRES-3C). The effects of using a mutant 3Cpro with reduced catalytic activity or using two different mutant IRES elements (the wt GNRA tetraloop sequence GCGA converted, in the cDNA, to GAGA or GTTA) were analysed. For both serotypes, the P1-2A-mIRES-3C construct containing the inefficient GTTA mutant IRES produced the highest amount of processed capsid proteins. These products self-assembled to form FMDV empty capsid particles, which have a related, but distinct, morphology (as determined by electron microscopy and reconstruction) from that determined previously by X-ray crystallography. The assembled empty capsids bind, in a divalent cation-dependent manner, to the RGD-dependent integrin αvβ6, a cellular receptor for FMDV, and are recognized appropriately in serotype-specific antigen ELISAs.

scholarly journals Sec62 Regulates Endoplasmic Reticulum Stress and Autophagy Balance to Affect Foot-and-Mouth Disease Virus Replication

2021 ◽  
Vol 11 ◽  
Author(s):  
Jin’en Wu ◽  
Zhihui Zhang ◽  
Zhidong Teng ◽  
Sahibzada Waheed Abdullah ◽  
Shiqi Sun ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Jnk Pathway ◽  
Fmdv Infection ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Fmdv Replication

Endoplasmic reticulum (ER) stress-induced autophagy is closely associated with viral infection and propagation. However, the intrinsic link between ER stress, autophagy, and viral replication during foot-and-mouth disease virus (FMDV) infection is not fully elucidated. Our previous studies demonstrated that FMDV infection activated the ER stress-associated UPR of the PERK-eIF2a and ATF6 signaling pathway, whereas the IRE1a signaling was suppressed. We found that the activated-ATF6 pathway participated in FMDV-induced autophagy and FMDV replication, while the IRE1α pathway only affected FMDV replication. Further studies indicated that Sec62 was greatly reduced in the later stages of FMDV infection and blocked the activation of the autophagy-related IRE1α-JNK pathway. Moreover, it was also found that Sec62 promoted IRE1a phosphorylation and negatively regulated FMDV proliferation. Importantly, Sec62 may interact with LC3 to regulate ER stress and autophagy balance and eventually contribute to FMDV clearance via fusing with lysosomes. Altogether, these results suggest that Sec62 is a critical molecule in maintaining and recovering ER homeostasis by activating the IRE1α-JNK pathway and delivering autophagosome into the lysosome, thus providing new insights on FMDV-host interactions and novel antiviral therapies.

scholarly journals Effective inhibition of foot-and-mouth disease virus (FMDV) replication in vitro by vector-delivered microRNAs targeting the 3D gene

2011 ◽  
Vol 8 (1) ◽  
pp. 292 ◽  
Author(s):  
Junzheng Du ◽  
Shandian Gao ◽  
Jihuai Luo ◽  
Guofeng Zhang ◽  
Guozheng Cong ◽  
...  
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Mouth Disease Virus ◽  
Effective Inhibition ◽  
Foot And Mouth ◽  
Fmdv Replication ◽  
3D Gene

scholarly journals Foot-and-Mouth Disease Virus Replicates Only Transiently in Well-Differentiated Porcine Nasal Epithelial Cells

2010 ◽  
Vol 84 (18) ◽  
pp. 9149-9160 ◽  
Author(s):  
Pradyot Dash ◽  
Paul V. Barnett ◽  
Michael S. Denyer ◽  
Terry Jackson ◽  
Catrina M. A. Stirling ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Progeny Virus ◽  
Dependent Manner ◽  
Apical Side ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACT Three-dimensional (3D) porcine nasal mucosal and tracheal mucosal epithelial cell cultures were developed to analyze foot-and-mouth disease virus (FMDV) interactions with mucosal epithelial cells. The cells in these cultures differentiated and polarized until they closely resemble the epithelial layers seen in vivo. FMDV infected these cultures predominantly from the apical side, primarily by binding to integrin αvβ6, in an Arg-Gly-Asp (RGD)-dependent manner. However, FMDV replicated only transiently without any visible cytopathic effect (CPE), and infectious progeny virus could be recovered only from the apical side. The infection induced the production of beta interferon (IFN-β) and the IFN-inducible gene Mx1 mRNA, which coincided with the disappearance of viral RNA and progeny virus. The induction of IFN-β mRNA correlated with the antiviral activity of the supernatants from both the apical and basolateral compartments. IFN-α mRNA was constitutively expressed in nasal mucosal epithelial cells in vitro and in vivo. In addition, FMDV infection induced interleukin 8 (IL-8) protein, granulocyte-macrophage colony-stimulating factor (GM-CSF), and RANTES mRNA in the infected epithelial cells, suggesting that it plays an important role in modulating the immune response.

scholarly journals Cellular Vimentin Interacts with Foot-and-Mouth Disease Virus Nonstructural Protein 3A and Negatively Modulates Viral Replication

2020 ◽  
Vol 94 (16) ◽  
Author(s):  
Xueqing Ma ◽  
Ying Ling ◽  
Pinghua Li ◽  
Pu Sun ◽  
Yimei Cao ◽  
...  
Keyword(s):  
Disease Virus ◽  
Virus Replication ◽  
Nonstructural Protein ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Amino Acid Residues ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Fmdv Replication

ABSTRACT Nonstructural protein 3A of foot-and-mouth disease virus (FMDV) is a partially conserved protein of 153 amino acids that is in most FMDVs examined to date, and it plays important roles in virus replication, virulence, and host range. To better understand the role of 3A during FMDV infection, we used coimmunoprecipitation followed by mass spectrometry to identify host proteins that interact with 3A in FMDV-infected cells. Here, we report that cellular vimentin is a host binding partner for 3A. The 3A-vimentin interaction was further confirmed by coimmunoprecipitation, glutathione S-transferase (GST) pull down, and immunofluorescence assays. Alanine-scanning mutagenesis indicated that amino acid residues 15 to 21 at the N-terminal region of the FMDV 3A are responsible for the interaction between 3A and vimentin. Using reverse genetics, we demonstrate that mutations in 3A that disrupt the interaction between 3A and vimentin are also critical for virus growth. Overexpression of vimentin significantly suppressed the replication of FMDV, whereas knockdown of vimentin significantly enhanced FMDV replication. However, chemical disruption of the vimentin network by acrylamide resulted in a significant decrease in viral yield, suggesting that an intact vimentin network is needed for FMDV replication. These results indicate that vimentin interacts with FMDV 3A and negatively regulates FMDV replication and that the vimentin-3A interaction is essential for FMDV replication. This study provides information that should be helpful for understanding the molecular mechanism of FMDV replication. IMPORTANCE Foot-and-mouth disease virus (FMDV) nonstructural protein 3A plays important roles in virus replication, host range, and virulence. To further understand the role of 3A during FMDV infection, identification of host cell factors that interact with FMDV 3A is needed. Here, we found that vimentin is a direct binding partner of FMDV 3A, and manipulation of vimentin has a negative effect on virus replication. We also demonstrated that amino acid residues 15 to 21 at the N-terminal region of the FMDV 3A are responsible for the interaction between 3A and vimentin and that the 3A-vimentin interaction is critical for viral replication since the full-length cDNA clone harboring mutations in 3A, which were disrupt 3A-vimentin reactivity, could not produce viable virus progeny. This study provides information that not only provides us a better understanding of the mechanism of FMDV replication but also helps in the development of novel antiviral strategies in the future.

Sign in / Sign up

Export Citation Format

Share Document