scholarly journals Foot-and-Mouth Disease Virus Capsid Protein VP1 Interacts with Host Ribosomal Protein SA To Maintain Activation of the MAPK Signal Pathway and Promote Virus Replication

2019 ◽  
Vol 94 (3) ◽  
Author(s):  
Zixiang Zhu ◽  
Weiwei Li ◽  
Xiangle Zhang ◽  
Congcong Wang ◽  
Lili Gao ◽  
...  
Keyword(s):  
Virus Replication ◽  
Mapk Pathway ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Fmdv Infection ◽  
Pathway Activation ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Fmdv Replication ◽  
Mapk Signal Pathway

ABSTRACT Foot-and-mouth disease virus (FMDV) is the causative agent of foot-and-mouth disease, a highly contagious, economically important viral disease. The structural protein VP1 plays significant roles during FMDV infection. Here, we identified that VP1 interacted with host ribosomal protein SA (RPSA). RPSA is a viral receptor for dengue virus and classical swine fever virus infections. However, the incubation of susceptible cells using the anti-RPSA antibodies did not block the infection of FMDV. Overexpression of porcine RPSA in the insusceptible cells could not trigger FMDV infection, suggesting that RPSA was not responsible for FMDV entry and infection. On the contrary, we found that overexpression of RPSA suppressed FMDV replication, and knockdown of RPSA enhanced FMDV replication. We further determined that FMDV infection activated the mitogen-activated protein kinase (MAPK) pathway and demonstrated that MAPK pathway activation was critically important for FMDV replication. RPSA negatively regulated MAPK pathway activation during FMDV infection and displayed an antiviral function. FMDV VP1 interacted with RPSA to abrogate the RPSA-mediated suppressive role in MAPK pathway activation. Together, our study indicated that MAPK pathway activation was required for FMDV replication and that host RPSA played a negatively regulatory role on MAPK pathway activation to suppress FMDV replication. FMDV VP1 bound to RPSA to promote viral replication by repressing RPSA-mediated function and maintaining the activation of MAPK signal pathway. IMPORTANCE Identification of virus-cell interactions is essential for making strategies to limit virus replication and refine the models of virus replication. This study demonstrated that FMDV utilized the MAPK pathway for viral replication. The host RPSA protein inhibited FMDV replication by suppressing the activation of the MAPK pathway during FMDV infection. FMDV VP1 bound to RPSA to repress the RPSA-mediated regulatory effect on MAPK pathway activation. This study revealed an important implication of the MAPK pathway for FMDV infection and identified a novel mechanism by which FMDV VP1 has evolved to interact with RPSA and maintain the activation of the MAPK pathway, elucidating new information regarding the signal reprogramming of host cells by FMDV.

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 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.

scholarly journals Proteomics Analysis of Porcine Serum Proteins by LC-MS/MS after Foot-and-Mouth Disease Virus (FMDV) Infection

2011 ◽  
Vol 73 (12) ◽  
pp. 1569-1572 ◽  
Author(s):  
Yongjie LIU ◽  
Keshan ZHANG ◽  
Haixue ZHENG ◽  
Youjun SHANG ◽  
Jianhong GUO ◽  
...  
Keyword(s):  
Disease Virus ◽  
Serum Proteins ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Proteomics Analysis ◽  
Porcine Serum ◽  
Fmdv Infection ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals The Foot-and-Mouth Disease Carrier State Divergence in Cattle

2016 ◽  
Vol 90 (14) ◽  
pp. 6344-6364 ◽  
Author(s):  
Carolina Stenfeldt ◽  
Michael Eschbaumer ◽  
Steven I. Rekant ◽  
Juan M. Pacheco ◽  
George R. Smoliga ◽  
...  
Keyword(s):  
Foot And Mouth Disease ◽  
Antiviral Response ◽  
Carrier State ◽  
Gamma Interferon ◽  
Mouth Disease ◽  
Fmdv Infection ◽  
Mouth Disease Virus ◽  
Follicle Associated Epithelium ◽  
Foot And Mouth ◽  
Host Antiviral Response

ABSTRACTThe pathogenesis of persistent foot-and-mouth disease virus (FMDV) infection was investigated in 46 cattle that were either naive or had been vaccinated using a recombinant, adenovirus-vectored vaccine 2 weeks before challenge. The prevalence of FMDV persistence was similar in both groups (62% in vaccinated cattle, 67% in nonvaccinated cattle), despite vaccinated cattle having been protected from clinical disease. Analysis of antemortem infection dynamics demonstrated that the subclinical divergence between FMDV carriers and animals that cleared the infection had occurred by 10 days postinfection (dpi) in vaccinated cattle and by 21 dpi in nonvaccinated animals. The anatomic distribution of virus in subclinically infected, vaccinated cattle was restricted to the pharynx throughout both the early and the persistent phases of infection. In nonvaccinated cattle, systemically disseminated virus was cleared from peripheral sites by 10 dpi, while virus selectively persisted within the nasopharynx of a subset of animals. The quantities of viral RNA shed in oropharyngeal fluid during FMDV persistence were similar in vaccinated and nonvaccinated cattle. FMDV structural and nonstructural proteins were localized to follicle-associated epithelium of the dorsal soft palate and dorsal nasopharynx in persistently infected cattle. Host transcriptome analysis of tissue samples processed by laser capture microdissection indicated suppression of antiviral host factors (interferon regulatory factor 7, CXCL10 [gamma interferon-inducible protein 10], gamma interferon, and lambda interferon) in association with persistent FMDV. In contrast, during the transitional phase of infection, the level of expression of IFN-λ mRNA was higher in follicle-associated epithelium of animals that had cleared the infection. This work provides novel insights into the intricate mechanisms of FMDV persistence and contributes to further understanding of this critical aspect of FMDV pathogenesis.IMPORTANCEThe existence of a prolonged, asymptomatic carrier state is a political impediment for control and potential eradication of foot-and-mouth disease (FMD). When FMD outbreaks occur, they are often extinguished by massive depopulation of livestock due to the fear that some animals may have undiagnosed subclinical infection, despite uncertainty over the biological relevance of FMD virus (FMDV) persistence. The work described here elucidates aspects of the FMDV carrier state in cattle which may facilitate identification and/or abrogation of asymptomatic FMDV infection. The divergence between animals that clear infection and those that develop persistent infection was demonstrated to occur earlier than previously established. The host antiviral response in tissues maintaining persistent FMDV was downregulated, whereas upregulation of IFN-λ mRNA was found in the epithelium of cattle that had recently cleared the infection. This suggests that the clearing of FMDV infection is associated with an enhanced mucosal antiviral response, whereas FMDV persistence is associated with suppression of the host antiviral response.

Establishment of persistent foot-and-mouth disease virus (FMDV) infection in MDBK cells

2015 ◽  
Vol 160 (10) ◽  
pp. 2503-2516 ◽  
Author(s):  
Lela Kopliku ◽  
Anthony Relmy ◽  
Aurore Romey ◽  
Kamila Gorna ◽  
Stephan Zientara ◽  
...  
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Fmdv Infection ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Mdbk Cells

scholarly journals Foot‐and‐mouth disease virus nonstructural protein 2B interacts with cyclophilin A, modulating virus replication

2018 ◽  
Vol 32 (12) ◽  
pp. 6706-6723 ◽  
Author(s):  
Huisheng Liu ◽  
Qiao Xue ◽  
Weijun Cao ◽  
Fan Yang ◽  
Linna Ma ◽  
...  
Keyword(s):  
Disease Virus ◽  
Virus Replication ◽  
Nonstructural Protein ◽  
Foot And Mouth Disease ◽  
Cyclophilin A ◽  
Mouth Disease ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Gold Nanoparticles Impair Foot-and-Mouth Disease Virus Replication

2016 ◽  
Vol 15 (1) ◽  
pp. 34-40 ◽  
Author(s):  
Solmaz Rafiei ◽  
Seyedeh Elham Rezatofighi ◽  
Mohammad Roayaei Ardakani ◽  
Saadat Rastegarzadeh
Keyword(s):  
Gold Nanoparticles ◽  
Disease Virus ◽  
Virus Replication ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Mouth Disease Virus ◽  
Foot And Mouth

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 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 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.

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