scholarly journals Membrane interactions and uncoating of Aichi virus, a picornavirus that lacks a VP4

2022 ◽  
Author(s):  
James Kelly ◽  
Jessica Swanson ◽  
Joseph Newman ◽  
Elisabetta Groppelli ◽  
Nicola Stonehouse ◽  
...  
Keyword(s):  
Pore Formation ◽  
Sequence Similarity ◽  
Critical Role ◽  
Foot And Mouth Disease ◽  
Model Membranes ◽  
Aichi Virus ◽  
Membrane Interactions ◽  
Membrane Pore ◽  
Animal Pathogens ◽  
Mouth Disease Virus

Kobuviruses are an unusual and poorly characterised genus within the picornavirus family, and can cause gastrointestinal enteric disease in humans, livestock and pets. The human Kobuvirus, Aichi virus (AiV) can cause severe gastroenteritis and deaths in children below the age of five years, however this is a very rare occurrence. During the assembly of most picornaviruses (e.g. poliovirus, rhinovirus and foot-and-mouth disease virus), the capsid precursor protein VP0 is cleaved into VP4 and VP2. However, Kobuviruses retain an uncleaved VP0. From studies with other picornaviruses, it is known that VP4 performs the essential function of pore formation in membranes, which facilitates transfer of the viral genome across the endosomal membrane and into the cytoplasm for replication. Here, we employ genome exposure and membrane interaction assays to demonstrate that pH plays a critical role in AiV uncoating and membrane interactions. We demonstrate that incubation at low pH alters the exposure of hydrophobic residues within the capsid, enhances genome exposure and enhances permeabilisation of model membranes. Furthermore, using peptides we demonstrate that the N-terminus of VP0 mediates membrane pore formation in model membranes, indicating that this plays an analogous function to VP4. Importance: To initiate infection, viruses must enter a host cell and deliver their genome into the appropriate location. The picornavirus family of small non-enveloped RNA viruses includes significant human and animal pathogens and are also models to understand the process of cell entry. Most picornavirus capsids contain the internal protein VP4, generated from cleavage of a VP0 precursor. During entry, VP4 is released from the capsid. In enteroviruses this forms a membrane pore, which facilitates genome release into the cytoplasm. Due to high levels of sequence similarity, it is expected to play the same role for other picornaviruses. Some picornaviruses, such as Aichi virus, retain an intact VP0, and it is unknown how these viruses re-arrange their capsids and induce membrane permeability in the absence of VP4. Here we have used Aichi virus as a model VP0 virus to test for conservation of function between VP0 and VP4. This could enhance understanding of pore function and lead to development of novel therapeutic agents that block entry.

scholarly journals High-Efficiency Utilization of the Bovine Integrin αvβ3 as a Receptor for Foot-and-Mouth Disease Virus Is Dependent on the Bovine β3Subunit

2000 ◽  
Vol 74 (16) ◽  
pp. 7298-7306 ◽  
Author(s):  
Sherry Neff ◽  
Peter W. Mason ◽  
Barry Baxt
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Disease Virus ◽  
Sequence Similarity ◽  
Foot And Mouth Disease ◽  
Viral Proteins ◽  
Mouth Disease ◽  
Amino Acid Sequence Similarity ◽  
Mouth Disease Virus ◽  
Human Integrin

ABSTRACT We have previously reported that Foot-and-mouth disease virus (FMDV), which is virulent for cattle and swine, can utilize the integrin αvβ3 as a receptor on cultured cells. Since those studies were performed with the human integrin, we have molecularly cloned the bovine homolog of the integrin αvβ3 and have compared the two receptors for utilization by FMDV. Both the αv and β3subunits of the bovine integrin have high degrees of amino acid sequence similarity to their corresponding human subunits in the ectodomains (96%) and essentially identical transmembrane and cytoplasmic domains. Within the putative ligand-binding domains, the bovine and human αv subunits have a 98.8% amino acid sequence similarity while there is only a 93% similarity between the β3 subunits of these two species. COS cell cultures, which are not susceptible to FMDV infection, become susceptible if cotransfected with αv and β3 subunit cDNAs from a bovine or human source. Cultures cotransfected with the bovine αvβ3 subunit cDNAs and infected with FMDV synthesize greater amounts of viral proteins than do infected cultures cotransfected with the human integrin subunits. Cells cotransfected with a bovine αv subunit and a human β3subunit synthesize viral proteins at levels equivalent to those in cells expressing both human subunits. However, cells cotransfected with the human αv and the bovine β3 subunits synthesize amounts of viral proteins equivalent to those in cells expressing both bovine subunits, indicating that the bovine β3 subunit is responsible for the increased effectiveness of this receptor. By engineering chimeric bovine-human β3subunits, we have shown that this increase in receptor efficiency is due to sequences encoding the C-terminal one-third of the subunit ectodomain, which contains a highly structured cysteine-rich repeat region. We postulate that amino acid sequence differences within this region may be responsible for structural differences between the human and bovine β3 subunit, leading to more efficient utilization of the bovine receptor by this bovine pathogen.

scholarly journals An infectious recombinant foot-and-mouth disease virus expressing a fluorescent marker protein

2013 ◽  
Vol 94 (7) ◽  
pp. 1517-1527 ◽  
Author(s):  
Julian Seago ◽  
Nicholas Juleff ◽  
Katy Moffat ◽  
Stephen Berryman ◽  
John M. Christie ◽  
...  
Keyword(s):  
Disease Virus ◽  
Reverse Genetics ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Marker Protein ◽  
Fluorescent Marker ◽  
Fmdv Infection ◽  
Animal Pathogens ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Foot-and-mouth disease virus (FMDV) is one of the most extensively studied animal pathogens because it remains a major threat to livestock economies worldwide. However, the dynamics of FMDV infection are still poorly understood. The application of reverse genetics provides the opportunity to generate molecular tools to further dissect the FMDV life cycle. Here, we have used reverse genetics to determine the capsid packaging limitations for a selected insertion site in the FMDV genome. We show that exogenous RNA up to a defined length can be stably introduced into the FMDV genome, whereas larger insertions are excised by recombination events. This led us to construct a recombinant FMDV expressing the fluorescent marker protein, termed iLOV. Characterization of infectious iLOV-FMDV showed the virus has a plaque morphology and rate of growth similar to the parental virus. In addition, we show that cells infected with iLOV-FMDV are easily differentiated by flow cytometry using the inherent fluorescence of iLOV and that cells infected with iLOV-FMDV can be monitored in real-time with fluorescence microscopy. iLOV-FMDV therefore offers a unique tool to characterize FMDV infection in vitro, and its applications for in vivo studies are discussed.

scholarly journals Evolutionary conserved compositional structures hidden in genomes of the foot-and-mouth disease virus and of the human rhinovirus

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Miguel Angel Fuertes ◽  
Silvia López-Arguello ◽  
Carlos Alonso
Keyword(s):  
Disease Virus ◽  
Sequence Similarity ◽  
Foot And Mouth Disease ◽  
Etiologic Agent ◽  
Mouth Disease ◽  
Human Rhinovirus ◽  
Nearest Neighbours ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Compositional Structures

Abstract Picornaviridae family includes several viruses of great economic and medical importance. Among all members of the family we focused our attention on the human rhinovirus, the most important etiologic agent of the common cold and on the foot-and-mouth disease virus that cause of an economically important disease in cattle. Despite the low sequence similarity of the polyprotein coding open reading frames of these highly divergent picornaviruses, they have in common structural and functional similarities including a similar genomic organization, a capsid structure composed of 60 copies of four different proteins, or 3D-structures showing similar general topology, among others. We hypothesized that such similarities could be reflected in emergent common compositional structures interspersed in their genomes which were not observed heretofore. Using a methodology categorizing nucleotide triplets by their gross-composition we have found two human rhinoviruses sharing compositional structures interspersed along their genomic RNA with three foot-and-mouth disease viruses. The shared compositional structures are in one case composed by nucleotide triplets containing all nearest-neighbours of A and G and in other case containing all nearest-neighbours of A, and C. The structures are under strong evolutionary constraints for variability, allowing the access to novel viral genomic motifs with likely biological relevance. The conserved fragments would be useful to predict critical mutation points sites important from the evolutionary point of view.

A critical role of N-myc and STAT interactor (Nmi) in foot-and-mouth disease virus (FMDV) 2C-induced apoptosis

2012 ◽  
Vol 170 (1-2) ◽  
pp. 59-65 ◽  
Author(s):  
Jianchang Wang ◽  
Yongqiang Wang ◽  
Jue Liu ◽  
Lin Ding ◽  
Quanhong Zhang ◽  
...  
Keyword(s):  
Disease Virus ◽  
Critical Role ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Induced Apoptosis

scholarly journals Serological and Molecular Investigation of Foot and Mouth Disease Virus and other animal pathogens at the Interface of Akagera National Park and Surrounding Cattle Farms between 2017 and 2020

2021 ◽  
Author(s):  
Jean Claude C Udahemuka ◽  
Gabriel Oluga Aboge ◽  
George Ogello Obiero ◽  
Angelique Ingabire ◽  
Natasha Beeton ◽  
...  
Keyword(s):  
Disease Virus ◽  
Rna Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Molecular Diagnostic ◽  
Diagnostic Tools ◽  
Rt Pcr ◽  
Animal Pathogens ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Background: Foot-and-Mouth Disease Virus (FMDV) is a positive-sense RNA virus of the family of the picornaviride and responsible for the disease with the highest economic impact, the Foot-and-Mouth Disease (FMD). FMD is endemic in Rwanda but there are gaps in knowing the seroprevalence and molecular epidemiology. This study reports the FMD seroprevalence and molecular characterization of FMDV in Eastern Rwanda. Surveillance in FMDV wild reservoirs, the African buffaloes, was also carried out revealing the presence of other pathogens and commensals. Results: The overall seroprevalence of FMD in the study area is at 9.36% in cattle and 2.65% in goats. We detected FMDV using molecular diagnostic tools such as RT-PCR and RT-LAMP and the phylogenetic analysis of the obtained sequences revealed the presence of serotype SAT 2, lineage II. Sequencing of oropharyngeal fluids collected from African buffaloes revealed the presence of several pathogens and commensals but no FMDV was detected in buffaloes. The plethora of pathogens identified from the buffalo gut gives an idea of the health challenges faced by cattle keepers in Eastern Rwanda due to possible cross infectivity on wildlife-domestic animals interface regions. Conclusions: We recommend further studies to focus on sampling more African buffaloes since the number sampled was statistically insignificant to conclusively exclude the presence or absence of FMDV in Eastern Rwanda buffaloes. The use of RT-PCR alongside RT-LAMP demonstrates that the latter can be adopted in endemic areas such as Rwanda to fill in the gaps in terms of molecular diagnostics. The identification of lineage II of SAT 2 in Rwanda for the first time shows that the pools as previously established are not static over time.

scholarly journals Foot-and-mouth disease virus VP1 target the MAVS to inhibit type-I interferon signaling and VP1 E83K mutation results in virus attenuation

2020 ◽  
Vol 16 (11) ◽  
pp. e1009057
Author(s):  
Pathum Ekanayaka ◽  
Seo-Yong Lee ◽  
Thilina U. B. Herath ◽  
Jae-Hoon Kim ◽  
Tae-Hwan Kim ◽  
...  
Keyword(s):  
Cell Culture ◽  
Disease Virus ◽  
Critical Role ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Type I ◽  
Wild Type ◽  
Humoral Immune ◽  
Mouth Disease Virus ◽  
Foot And Mouth

VP1, a pivotal capsid protein encoded by the foot-and-mouth disease virus (FMDV), plays an important role in receptor-mediated attachment and humoral immune responses. Previous studies show that amino acid changes in the VP1 protein of cell culture-adapted strains of FMDV alter the properties of the virus. In addition, FMDV VP1 modulates host IFN signal transduction. Here, we examined the ability of cell culture-adapted FMDV VP1(83K) and wild-type FMDV VP1(83E) to evade host immunity by blocking mitochondrial antiviral signaling protein (MAVS)/TNF Receptor Associated Factor 3 (TRAF3) mediated cellular innate responses. Wild-type FMDV VP1(83E) interacted specifically with C-terminal TRAF3-binding site within MAVS and this interaction inhibited binding of TRAF3 to MAVS, thereby suppressing interferon-mediated responses. This was not observed for cell culture-adapted FMDV VP1(83K). Finally, chimeric FMDV harboring VP1(83K) showed very low pathogenicity in pigs. Collectively, these data highlight a critical role of VP1 with respect to suppression of type-I IFN pathway and attenuation of FMDV by the E83K mutation in VP1.

Identification of novel interactions between host and non-structural protein 2C of foot-and-mouth disease virus

2021 ◽  
Author(s):  
Sonalika Mahajan ◽  
Gaurav Kumar Sharma ◽  
Kavita Bora ◽  
Bramhadev Pattnaik
Keyword(s):  
Disease Virus ◽  
Critical Role ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Structural Protein ◽  
Host Proteins ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Novel Interactions ◽  
Two Hybrid

The 2C protein of foot-and-mouth disease virus (FMDV) is reported to play a critical role in the virus replication complex and modulating the host’s immune response. However, the underlying molecular intricacies of subversion of cellular machinery remains poorly understood, thus emphasizing the need to study 2C-host interactions. In this study, we identified the host proteins interacting with the 2C using yeast-two hybrid (Y2H) approach, which is one of the most recognized, high-throughput tools to study protein-protein interactions. The FMDV-2C bait was characterized for auto-activation, toxicity, and expression and was found to be suitable for mating with cDNA library. On preliminary screening a total of 32 interacting host proteins were identified which were reduced to 22 on subsequent confirmation with alternative yeast based assays. Amongst these, NMI/2C interaction has been reported earlier by Wang et al. (2012) and remaining 21 are novel interactions. The Reactome analysis has revealed the role of the identified host proteins in cellular pathways exploited by 2C during FMDV replication. We also confirmed interaction of MARCH7, an E3 ubiquitin ligase with 2C using mammalian two-hybrid system and co-immunoprecipitation. This study leads to the identification of novel 2C interacting host proteins which enhance our understanding of 2C-host interface and may provide checkpoints for development of potential therapeutics against FMDV.

scholarly journals The Early Protective Thymus-Independent Antibody Response to Foot-and-Mouth Disease Virus Is Mediated by Splenic CD9+ B Lymphocytes

2007 ◽  
Vol 81 (17) ◽  
pp. 9357-9367 ◽  
Author(s):  
Matias Ostrowski ◽  
Monica Vermeulen ◽  
Osvaldo Zabal ◽  
Patricia I. Zamorano ◽  
Ana M. Sadir ◽  
...  
Keyword(s):  
Antibody Response ◽  
B Lymphocytes ◽  
Disease Virus ◽  
Neutralizing Antibodies ◽  
Critical Role ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Immunoglobulin M ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACT Infection of mice with cytopathic foot-and-mouth disease virus (FMDV) induces a rapid and specific thymus-independent (TI) neutralizing antibody response that promptly clears the virus. Herein, it is shown that FMDV-infected dendritic cells (DCs) directly stimulate splenic innate-like CD9+ B lymphocytes to rapidly (3 days) produce neutralizing anti-FMDV immunoglobulin M antibodies without T-lymphocyte collaboration. In contrast, neither follicular (CD9−) B lymphocytes from the spleen nor B lymphocytes from lymph nodes efficiently respond to stimulation with FMDV-infected DCs. The production of these protective neutralizing antibodies is dependent on DC-derived interleukin-6 (IL-6) and on CD9+ cell-derived IL-10 secretion. In comparison, DCs loaded with UV-inactivated FMDV are significantly less efficient in directly stimulating B lymphocytes to secrete TI antibodies. A critical role of the spleen in the early production of anti-FMDV antibodies in infected mice was also demonstrated in vivo. Indeed, either splenectomy or functional disruption of the marginal zone of the spleen delays and reduces the magnitude of the TI anti-FMDV antibody response in infected mice. Together, these results indicate that in addition to virus localization, the FMDV-mediated modulation of DC functionality is a key parameter that collaborates in the induction of a rapid and protective TI antibody response against this virus.

scholarly journals shRNA transgenic swine display resistance to infection with the foot-and-mouth disease virus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenping Hu ◽  
Haixue Zheng ◽  
Qiuyan Li ◽  
Yuhang Wang ◽  
Xiangtao Liu ◽  
...  
Keyword(s):  
Disease Virus ◽  
Nonstructural Protein ◽  
Clinical Signs ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Viral Rna ◽  
Animal Pathogens ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Transgenic Cells

AbstractFoot-and-mouth disease virus (FMDV) is one of the most important animal pathogens in the world. FMDV naturally infects swine, cattle, and other cloven-hoofed animals. FMD is not adequately controlled by vaccination. An alternative strategy is to develop swine that are genetically resistant to infection. Here, we generated FMDV-specific shRNA transgenic cells targeting either nonstructural protein 2B or polymerase 3D of FMDV. The shRNA-positive transgenic cells displayed significantly lower viral production than that of the control cells after infection with FMDV (P < 0.05). Twenty-three transgenic cloned swine (TGCS) and nine non-transgenic cloned swine (Non-TGCS) were produced by somatic cell nuclear transfer (SCNT). In the FMDV challenge study, one TGCS was completely protected, no clinical signs, no viremia and no viral RNA in the tissues, no non-structural antibody response, another one TGCS swine recovered after showing clinical signs for two days, whereas all of the normal control swine (NS) and Non-TGCS developed typical clinical signs, viremia and viral RNA was determined in the tissues, the non-structural antibody was determined, and one Non-TGCS swine died. The viral RNA load in the blood and tissues of the TGCS was reduced in both challenge doses. These results indicated that the TGCS displayed resistance to the FMDV infection. Immune cells, including CD3+, CD4+, CD8+, CD21+, and CD172+ cells, and the production of IFN-γ were analyzed, there were no significant differences observed between the TGCS and NS or Non-TGCS, suggesting that the FMDV resistance may be mainly derived from the RNAi-based antiviral pathway. Our work provides a foundation for a breeding approach to preventing infectious disease in swine.

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