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.

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

scholarly journals BothcisandtransActivities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication

2016 ◽  
Vol 90 (15) ◽  
pp. 6864-6883 ◽  
Author(s):  
Morgan R. Herod ◽  
Cristina Ferrer-Orta ◽  
Eleni-Anna Loundras ◽  
Joseph C. Ward ◽  
Nuria Verdaguer ◽  
...  
Keyword(s):  
Disease Virus ◽  
Viral Genome ◽  
Foot And Mouth Disease ◽  
Rna Replication ◽  
Mouth Disease ◽  
Viral Rna ◽  
Genome Replication ◽  
Replication Complex ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACTThePicornaviridaeis a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host-cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided intrans(i.e., via expression from a separate RNA molecule), while others are required incis(i.e., expressed from the template RNA molecule).In vitrostudies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymaticcis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that thiscis-acting role of 3D is distinct from the catalytic activity, which is predominantlytransacting. Immunofluorescence studies suggest that bothcis- andtrans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts inciswith RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further.IMPORTANCEFoot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome occurs within replication complexes, and understanding this process can facilitate the development of novel therapeutic strategies. Many of the nonstructural proteins involved in replication possess multiple functions in the viral life cycle, some of which can be supplied to the replication complex from a separate genome (i.e., intrans) while others must originate from the template (i.e., incis). Here, we present an analysis ofcisandtransactivities of the RNA-dependent RNA polymerase 3D. We demonstrate a novelcis-acting role of 3D in replication. Our data suggest that this role is distinct from its enzymatic functions and requires interaction with the viral genome. Our data further the understanding of genome replication of this important pathogen.

Delivery of a foot-and-mouth disease virus empty capsid subunit antigen with nonstructural protein 2B improves protection of swine

Vaccine ◽  
2008 ◽  
Vol 26 (45) ◽  
pp. 5689-5699 ◽  
Author(s):  
Lindomar Pena ◽  
Mauro Pires Moraes ◽  
Marla Koster ◽  
Thomas Burrage ◽  
Juan M. Pacheco ◽  
...  
Keyword(s):  
Disease Virus ◽  
Nonstructural Protein ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Empty Capsid ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals (F)uridylylated Peptides Linked to VPg1 of Foot-and- Mouth Disease Virus (FMDV): Design, Synthesis and X-Ray Crystallography of the Complexes with FMDV RNA-Dependent RNA Polymerase

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2360 ◽  
Author(s):  
Sonia de Castro ◽  
Cristina Ferrer-Orta ◽  
Alberto Mills ◽  
Gloria Fernández-Cureses ◽  
Federico Gago ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Viral Rna ◽  
Hydroxyl Group ◽  
Rna Dependent Rna Polymerase ◽  
X Ray ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Foot-and-mouth disease virus (FMDV) is an RNA virus belonging to the Picornaviridae family that contains three small viral proteins (VPgs), named VPg1, VPg2 and VPg3, linked to the 5′-end of the viral genome. These VPg proteins act as primers for RNA replication, which is initiated by the consecutive binding of two UMP molecules to the hydroxyl group of Tyr3 in VPg. This process, termed uridylylation, is catalyzed by the viral RNA-dependent RNA polymerase named 3Dpol. 5-Fluorouridine triphosphate (FUTP) is a potent competitive inhibitor of VPg uridylylation. Peptide analysis showed FUMP covalently linked to the Tyr3 of VPg. This fluorouridylylation prevents further incorporation of the second UMP residue. The molecular basis of how the incorporated FUMP blocks the incorporation of the second UMP is still unknown. To investigate the mechanism of inhibition of VPg uridylylation by FUMP, we have prepared a simplified 15-mer model of VPg1 containing FUMP and studied its x-ray crystal structure in complex with 3Dpol. Unfortunately, the fluorouridylylated VPg1 was disordered and not visible in the electron density maps; however, the structure of 3Dpol in the presence of VPg1-FUMP showed an 8 Å movement of the β9-α11 loop of the polymerase towards the active site cavity relative to the complex of 3Dpol with VPg1-UMP. The conformational rearrangement of this loop preceding the 3Dpol B motif seems to block the access of the template nucleotide to the catalytic cavity. This result may be useful in the design of new antivirals against not only FMDV but also other picornaviruses, since all members of this family require the uridylylation of their VPg proteins to initiate the viral RNA synthesis.

Diagnostic potential of recombinant nonstructural protein 3B to detect antibodies induced by foot-and-mouth disease virus infection in bovines

2014 ◽  
Vol 159 (9) ◽  
pp. 2359-2369 ◽  
Author(s):  
Amiya Kumar Mohapatra ◽  
Jajati Keshari Mohapatra ◽  
Laxmi Kant Pandey ◽  
Aniket Sanyal ◽  
Bramhadev Pattnaik
Keyword(s):  
Virus Infection ◽  
Disease Virus ◽  
Nonstructural Protein ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Diagnostic Potential ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals Foot-and-Mouth Disease Virus Nonstructural Protein 2C Interacts with Beclin1, Modulating Virus Replication

2012 ◽  
Vol 86 (22) ◽  
pp. 12080-12090 ◽  
Author(s):  
D. P. Gladue ◽  
V. O'Donnell ◽  
R. Baker-Branstetter ◽  
L. G. Holinka ◽  
J. M. Pacheco ◽  
...  
Keyword(s):  
Disease Virus ◽  
Virus Replication ◽  
Nonstructural Protein ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals Inter-laboratory comparison of 2 ELISA kits used for foot-and-mouth disease virus nonstructural protein serology

2020 ◽  
Vol 32 (6) ◽  
pp. 933-937
Author(s):  
Clare F. J. Browning ◽  
Antonello Di Nardo ◽  
Lissie Henry ◽  
Tim Pollard ◽  
Lynne Hendry ◽  
...  
Keyword(s):  
Disease Virus ◽  
Disease Surveillance ◽  
Nonstructural Protein ◽  
Foot And Mouth Disease ◽  
Screen Test ◽  
Mouth Disease ◽  
Nonstructural Proteins ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Thermo Fisher Scientific

Serologic assays used to detect antibodies to nonstructural proteins (NSPs) of foot-and-mouth disease virus (FMDV) are used for disease surveillance in endemic countries, and are essential to providing evidence for freedom of the disease with or without vaccination and to recover the free status of a country after an outbreak. In a 5-site inter-laboratory study, we compared the performance of 2 commercial NSP ELISA kits (ID Screen FMD NSP ELISA single day [short] and overnight protocols, ID.Vet; PrioCHECK FMDV NS antibody ELISA, Thermo Fisher Scientific). The overall concordance between the PrioCHECK and ID Screen test was 93.8% (95% CI: 92.0–95.2%) and 94.8% (95% CI: 93.1–96.1%) for the overnight and short ID Screen incubation protocols, respectively. Our results indicate that the assays (including the 2 different formats of the ID Screen test) can be used interchangeably in post-outbreak serosurveillance.

Sign in / Sign up

Export Citation Format

Share Document