scholarly journals Attenuated Foot-and-Mouth Disease Virus RNA Carrying a Deletion in the 3′ Noncoding Region Can Elicit Immunity in Swine

2009 ◽  
Vol 83 (8) ◽  
pp. 3475-3485 ◽  
Author(s):  
Miguel Rodríguez Pulido ◽  
Francisco Sobrino ◽  
Belén Borrego ◽  
Margarita Sáiz

ABSTRACT We constructed foot-and-mouth disease virus (FMDV) mutants bearing independent deletions of the two stem-loop structures predicted in the 3′ noncoding region of viral RNA, SL1 and SL2, respectively. Deletion of SL2 was lethal for viral infectivity in cultured cells, while deletion of SL1 resulted in viruses with slower growth kinetics and downregulated replication associated with impaired negative-strand RNA synthesis. With the aim of exploring the potential of an RNA-based vaccine against foot-and-mouth disease using attenuated viral genomes, full-length chimeric O1K/C-S8 RNAs were first inoculated into pigs. Our results show that FMDV viral transcripts could generate infectious virus and induce disease in swine. In contrast, RNAs carrying the ΔSL1 mutation on an FMDV O1K genome were innocuous for pigs but elicited a specific immune response including both humoral and cellular responses. A single inoculation with 500 μg of RNA was able to induce a neutralizing antibody response. This response could be further boosted by a second RNA injection. The presence of the ΔSL1 mutation was confirmed in viruses isolated from serum samples of RNA-inoculated pigs or after transfection and five passages in cell culture. These findings suggest that deletion of SL1 might contribute to FMDV attenuation in swine and support the potential of RNA technology for the design of new FMDV vaccines.

Vaccine ◽  
2011 ◽  
Vol 29 (52) ◽  
pp. 9655-9662 ◽  
Author(s):  
Miguel A. Martín-Acebes ◽  
Ángela Vázquez-Calvo ◽  
Mónica González-Magaldi ◽  
Francisco Sobrino

2001 ◽  
Vol 75 (1) ◽  
pp. 527-532 ◽  
Author(s):  
Sherry Neff ◽  
Barry Baxt

ABSTRACT The integrin αvβ3 has been shown to function as one of the integrin receptors on cultured cells for foot-and-mouth disease virus (FMDV), and high-efficiency utilization of the bovine homolog of this integrin is dependent on the cysteine-rich repeat region of the bovine β3 subunit. In this study we have examined the role of the cytoplasmic domains of the αv and β3 subunits in FMDV infection. We have found that truncations or extensions of these domains of either subunit, including deletions removing almost all of the cytoplasmic domains, had little or no effect on the ability of the integrin to function as a receptor for FMDV. The lysosomotropic agent monensin inhibited viral replication in cells transfected with either intact or cytoplasmic domain-truncated αvβ3. In addition, viral replication in transfected cells was inhibited by an αvβ3 function-blocking antibody but not by function-blocking antibodies to three other RGD-directed integrins, suggesting that these integrins are not involved in the infectious process. These results indicate that alterations to the cytoplasmic domains of either subunit, which lead to the inability of the integrin receptor to function normally, do not abolish the ability of the integrin to bind and internalize this viral ligand.


1996 ◽  
Vol 256 (2) ◽  
pp. 364-376 ◽  
Author(s):  
Nuria Verdaguer ◽  
Mauricio G. Mateu ◽  
Jerónimo Bravo ◽  
Esteban Domingo ◽  
Ignasi Fita

1996 ◽  
Vol 117 (2) ◽  
pp. 349-360 ◽  
Author(s):  
J. S. Salt ◽  
G. Mulcahy ◽  
R. P. Kitching

SummaryIsotype-specific antibody responses to foot-and-mouth disease virus (FMDV) were measured in the sera and upper respiratory tract secretions of vaccinated and susceptible cattle challenged with FMDV by direct contact or by intranasal inoculation. A comparison was made between cattle that eliminated FMDV and those that developed and maintained a persistent infection. Serological and mucosal antibody responses were detected in all animals after challenge. IgA and 1gM were detected before the development of IgG1and IgG2responses. 1gM was not detected in vaccinated cattle. Challenge with FMDV elicited a prolonged biphasic secretory antibody response in FMDV ‘carrier’ animals only. The response was detected as FMDVspecific IgA in both mucosal secretions and serum samples, which gained statistical significance (P< 0·05) by 5 weeks after challenge. This observation could represent the basis of a test to differentiate vaccinated and/or recovered convalescent cattle from FMDV ‘carriers’.


2020 ◽  
Author(s):  
Joseph C. Ward ◽  
Lidia Lasecka-Dykes ◽  
Chris Neil ◽  
Oluwapelumi Adeyemi ◽  
Sarah Gold ◽  
...  

AbstractThe positive stranded RNA genomes of picornaviruses comprise a single large open reading frame flanked by 5′ and 3′ untranslated regions (UTRs). Foot-and-mouth disease virus (FMDV) has an unusually large 5′ UTR (1.3 kb) containing five structural domains. These include the internal ribosome entry site (IRES), which facilitates initiation of translation, and the cis-acting replication element (cre). Less well characterised structures are a 5′ terminal 360 nucleotide stem-loop, a variable length poly-C-tract of approximately 100-200 nucleotides and a series of two to four tandemly repeated pseudoknots (PKs). We investigated the structures of the PKs by selective 2′ hydroxyl acetylation analysed by primer extension (SHAPE) analysis and determined their contribution to genome replication by mutation and deletion experiments. SHAPE and mutation experiments confirmed the importance of the previously predicted PK structures for their function. Deletion experiments showed that although PKs are not essential for replication, they provide genomes with a competitive advantage. However, although replicons and full-length genomes lacking all PKs were replication competent, no infectious virus was rescued from genomes containing less than one PK copy. This is consistent with our earlier report describing the presence of putative packaging signals in the PK region.


Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2203
Author(s):  
Umanga Gunasekara ◽  
Miranda R. Bertram ◽  
Do H. Dung ◽  
Bui H. Hoang ◽  
Nguyen T. Phuong ◽  
...  

The genetic diversity of foot-and-mouth disease virus (FMDV) poses a challenge to the successful control of the disease, and it is important to identify the emergence of different strains in endemic settings. The objective of this study was to evaluate the sampling of clinically healthy livestock at slaughterhouses as a strategy for genomic FMDV surveillance. Serum samples (n = 11,875) and oropharyngeal fluid (OPF) samples (n = 5045) were collected from clinically healthy cattle and buffalo on farms in eight provinces in southern and northern Vietnam (2015–2019) to characterize viral diversity. Outbreak sequences were collected between 2009 and 2019. In two slaughterhouses in southern Vietnam, 1200 serum and OPF samples were collected from clinically healthy cattle and buffalo (2017 to 2019) as a pilot study on the use of slaughterhouses as sentinel points in surveillance. FMDV VP1 sequences were analyzed using discriminant principal component analysis and time-scaled phylodynamic trees. Six of seven serotype-O and -A clusters circulating in southern Vietnam between 2017–2019 were detected at least once in slaughterhouses, sometimes pre-dating outbreak sequences associated with the same cluster by 4–6 months. Routine sampling at slaughterhouses may provide a timely and efficient strategy for genomic surveillance to identify circulating and emerging FMDV strains.


2017 ◽  
Vol 24 (8) ◽  
Author(s):  
Zezhong Liu ◽  
Junjun Shao ◽  
Furong Zhao ◽  
Guangqing Zhou ◽  
Shandian Gao ◽  
...  

ABSTRACT The potential diagnostic value of chemiluminescence immunoassays (CLIAs) has been accepted in recent years, although their use for foot-and-mouth disease (FMD) diagnostics has not been reported. Full-length 3ABC and 2C proteins were expressed in bacteria and purified by affinity chromatography to develop a rapid and accurate approach to distinguish pigs infected with foot-and-mouth disease virus (FMDV) from vaccinated pigs. The recombinant proteins were then used as antigens to develop two CLIAs for the detection of antibodies against nonstructural viral proteins. The diagnostic performance of the two assays was compared by analyzing serum from pigs (naive pigs, n = 63; vaccinated, uninfected pigs, n = 532; naive, infected pigs, n = 117) with a known infection status. The 3ABC-2C CLIA had a higher accuracy rate, with a diagnostic sensitivity of 100% and a diagnostic specificity of 96.5%, than the 3ABC CLIA, which had a diagnostic sensitivity of 95.7% and a diagnostic specificity of 96.0%. The results of the 3ABC-2C CLIA also had a high rate of concordance with those of two commercial FMDV enzyme-linked immunosorbent assay (ELISA) kits used to assess serum collected from 962 pigs in the field (96.2% and 97.8%, respectively). The 3ABC-2C CLIA detected infection in serum samples from infected pigs earlier than the commercial ELISA kits. In addition, the 3ABC-2C CLIA produced results within 15 min. On the basis of these findings, the 3ABC-2C CLIA could serve as the foundation for the development of penside FMD diagnostics and offers an alternative method to detect FMDV infections.


2003 ◽  
Vol 77 (3) ◽  
pp. 2243-2246 ◽  
Author(s):  
Laurence Tiley ◽  
Andrew M. Q. King ◽  
Graham J. Belsham

ABSTRACT A temperature-sensitive (ts) mutation was identified within the 5′-untranslated region of foot-and-mouth disease virus (FMDV) RNA. The mutation destabilizes a stem-loop structure recently identified as a cis-acting replication element (cre). Genetic analyses indicated that the ts defect in virus replication could be complemented. Thus, the FMDV cre can function in trans. It is suggested that the cre be renamed a 3B-uridylylation site (bus).


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