Into the Deep (Sequence) of the Foot-and-Mouth Disease Virus Gene Pool: Bottlenecks and Adaptation during Infection in Naive and Vaccinated Cattle.
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ABSTRACT:
SUBMITTER: Fish I
PROVIDER: S-EPMC7157448 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A time-course pathogenesis study was performed to compare and contrast primary foot-and-mouth disease virus (FMDV) infection following simulated-natural (intra-nasopharyngeal) virus exposure of cattle that were non-vaccinated or vaccinated using a recombinant adenovirus-vectored FMDV vaccine. FMDV genome and infectious virus were detected during the initial phase of infection in both categories of animals with consistent predilection for the nasopharyngeal mucosa. A rapid progression of infection with viremia and widespread dissemination of virus occurred in non-vaccinated animals whilst vaccinated cattle were protected from viremia and clinical FMD. Analysis of micro-anatomic distribution of virus during early infection by lasercapture microdissection localized FMDV RNA to follicle-associated epithelium of the nasopharyngeal mucosa in both groups of animals, with concurrent detection of viral genome in nasopharyngeal MALT follicles in vaccinated cattle only. FMDV structural and non-structural proteins were detected in epithelial cells of the nasopharyngeal mucosa by immunomicroscopy 24 hours after inoculation in both non-vaccinated and vaccinated steers. Co-localization of CD11c+/MHC II+ cells with viral protein occurred early at primary infection sites in vaccinated steers while similar host-virus interactions were observed at later time points in non-vaccinated steers. Additionally, numerous CD8+/CD3- host cells, representing presumptive natural killer cells, were observed in association with foci of primary FMDV infection in the nasopharyngeal mucosa of vaccinated steers but were absent in non-vaccinated steers. Immunomicroscopic evidence of an activated antiviral response at primary infection sites of vaccinated cattle was corroborated by a relative induction of interferon -α, -β, -γ and -λ mRNA in micro-dissected samples of nasopharyngeal mucosa. Although vaccination protected cattle from viremia and clinical FMD, there was subclinical infection of epithelial cells of the nasopharyngeal mucosa that could enable shedding and long-term persistence of infectious virus. Additionally, these data indicate different mechanisms within the immediate host response to infection between non-vaccinated and vaccinated cattle.
| S-EPMC4658095 | biostudies-literature
Project description:Control and eradication of foot-and-mouth disease (FMD) are impeded by the existence of a persistent, subclinical phase of infection in ruminants; animals with this status are referred to as carriers. However, the epidemiological significance of these FMD virus (FMDV) carriers is uncertain. In the current investigation, the contagion associated with FMDV carrier cattle was investigated by exposure of susceptible cattle and pigs to oropharyngeal fluid (OPF) samples or tissues harvested from persistently infected cattle. Naive cattle were inoculated through intranasopharyngeal deposition of unprocessed OPF samples that had been collected from FMDV carriers at 30 days postinfection. These inoculated cattle developed clinical FMD, and the severity of disease they developed was similar to that of animals that had been infected with a high-titer inoculum. In contrast, pigs exposed via intraoropharyngeal inoculation of the same OPF samples or via ingestion of nasopharyngeal tissues harvested from the same cohort of persistently infected cattle did not develop FMD. These findings indicate that there is demonstrable contagion associated with FMDV carrier cattle despite the lack of evidence for transmission by direct contact. The findings presented herein provide novel information that should be considered for FMD risk mitigation strategies.IMPORTANCE Foot-and-mouth disease (FMD) is a viral disease of livestock with substantial impact on agricultural production and subsistence farming on a global scale. Control of FMD is impeded by the existence of a prolonged asymptomatic carrier phase during which infected cattle shed low quantities of infectious virus in oropharyngeal fluid (OPF) for months to years after infection. The epidemiological significance of FMD virus (FMDV) carriers is unresolved. However, the existence of the FMDV carrier state has substantial impact on international trade in animal products. The current investigation demonstrated that transfer of OPF from persistently infected FMDV carrier cattle to naive cattle led to fulminant clinical FMD. It was thus demonstrated that, although the risk for disease transmission under natural conditions is considered to be low, there is detectable contagion associated with FMDV carrier cattle. This finding is important for optimization of FMD risk mitigation strategies.
| S-EPMC6135961 | biostudies-literature
Project description:Foot-and-mouth disease (FMD), caused by FMD virus (FMDV; Aphthovirus, Picornaviridae), is a highly contagious and economically important disease of cloven-hoofed domestic livestock and wildlife species worldwide. Subsequent to the clinical phase of FMD, a large proportion of FMDV-infected ruminants become persistently infected carriers, defined by detection of FMDV in oropharyngeal fluid (OPF) samples 28 days or more post-infection. The goal of this prospective study was to characterize the FMD carrier state in cattle subsequent to natural infection under typical husbandry practices in Vietnam. Ten persistently infected cattle on eight farms in the Long An province in southern Vietnam were monitored by monthly screening of serum and oropharyngeal fluid samples for 12 months. To assess transmission from FMDV carriers, 16 naïve cattle were intentionally brought into direct contact with the persistently infected animals for 6 months, and were monitored by clinical and laboratory methods. The restricted mean duration of the FMD carrier state was 27.7 months, and the rate of decrease of the proportion of carrier animals was 0.03 per month. There was no evidence of transmission to naïve animals throughout the study period. Additionally, there was no detection of FMDV infection or seroconversion in three calves born to carrier animals during the study. The force of infection for carrier-to-contact transmission was 0 per month, with upper 95% confidence limit of 0.064 per month. Phylogenetic analysis of viral protein 1 (VP1) coding sequences obtained from carriers indicated that all viruses recovered in this study belonged to the O/ME-SA/PanAsia lineage, and grouped phylogenetically with temporally and geographically related viruses. Analysis of within-host evolution of FMDV, based upon full-length open reading frame sequences recovered from consecutive samples from one animal, indicated that most of the non-synonymous changes occurred in Lpro, VP2, and VP3 protein coding regions. This study suggests that the duration of FMDV persistent infection in cattle may be longer than previously recognized, but the risk of transmission is low. Additional novel insights are provided into within-host viral evolution under natural conditions in an endemic setting.
| S-EPMC6072850 | biostudies-literature
Project description:We present the RNA-seq based transcriptome profile of ventral soft palate tissue from two Indian indigenous breeds (Malnad Gidda and Hallikar; Bos indicus) of cattle and Holstein Friesian (HF) crossbred calves. Differentially expressed gene pattern showed stronger innate immune response in the indigenous calves. We find that induction of innate and cell mediated immune response is associated with early viral clearance and mild form of foot-and-mouth disease.
2021-12-06 | GSE167574 | GEO
Project description:BACKGROUND:Foot-and-mouth disease virus (FMDV) is a highly contagious viral infection of large ruminants. Despite the massive application of vaccines against FMDV, several outbreaks are still being reported in Africa and Asia. AIM:To perform molecular characterization of FMDV in an outbreak among a cattle herd Saudi Arabia in 2016. This herd had been vaccinated with a polyvalent FMDV vaccine. METHODS:To investigate this outbreak, we collected specimens from 77 animals showing typical clinical signs of FMDV. Specimens including sera, nasal swabs, and tissues (tongue, coronary bands, hooves, and hearts) were collected. We tested the collected cattle sera for the presence of FMDV antibodies with commercial ELISA kits. In addition, we tested the swabs for the presence of the most common FMDV strains (O, A, Asia-1 and SAT-2) with RT-PCR using serotype-specific oligonucleotides. RESULTS:Serology showed that 22% of the tested sera were positive. Molecular testing of the examined swabs confirmed that 24% of the tested animals were positive. Our sequencing analysis confirmed that the circulating strains of FMDV belonged to FMDV serotype O. The phylogenetic tree based on the FMDV-VP-1 gene revealed high nucleotide identity between the circulating strains and the Bangladesh strain (99%). These strains were distinct (shared 89% nucleotide identity) from the FMDV-O strains used for the preparation of the vaccine administered to the animals in this herd. Moreover, they had 7% nucleotide difference between the FMDV-O strains reported in Saudi Arabian in 2013. CONCLUSION:More in-depth molecular characterization of these FMDV strains is warranted.
| S-EPMC6831000 | biostudies-literature
Project description:Immediate vaccination of the most susceptible and epidemiological relevant animals is a crucial part of control measures that facilitate virus elimination in case of entry of foot-and-mouth disease (FMD). The objective of this study was to evaluate the effect of cattle vaccination 7 and 14 days prior challenge using a vaccine commonly applied in systematic vaccination campaigns against transmission of FMD virus (FMDV). Transmission of FMDV was investigated in three groups of ten cattle each: one non-vaccinated group and two groups that were either vaccinated 7 days (-7/vaccinated group) or 14 days (-14/vaccinated group) before intranasal (IN) inoculation. Five cattle heads from each group were inoculated using the IN-route with the A/Argentina/2001 FMDV strain, while the remaining five cattle heads of each group were contact-exposed to inoculated cattle. Clinical signs were recorded; virus isolation and genome detection by RT-PCR were carried out on oesophageal-pharyngeal fluid (OPF) and blood. Neutralizing antibody titers and antibodies against non-structural proteins (NSP) of FMDV were also determined. Results suggest that the experimental design, virus challenge dose, and virus infectivity were appropriate and that the virus had been transmitted to naïve calves. Under the outlined experimental conditions, vaccination 7 and 14 days prior to challenge induced full clinical protection against virus inoculation. Moreover, -7/ or -14/vaccinated calves that had been contact-exposed to -7/ or -14/vaccinated IN-challenged calves, did not become infected. Consequently, no virus transmission occurred from vaccinated and subsequently infected calves to cohabitating vaccinated calves (R = 0). According to our results, early vaccination during an outbreak is effective as virus transmission can be significantly reduced using a vaccine commercially available, routinely applied in systematic vaccination campaigns.
| S-EPMC7190753 | biostudies-literature
Project description:Viral recombination contributes to the emergence of novel strains with the potential for altered host range, transmissibility, virulence, and immune evasion. For foot-and-mouth disease virus (FMDV), cell culture experiments and phylogenetic analyses of field samples have demonstrated the occurrence of recombination. However, the frequency of recombination and associated virus-host interactions within an infected host have not been determined. We have previously reported the detection of interserotypic recombinant FMDVs in oropharyngeal fluid (OPF) samples of 42% (5/12) of heterologously superinfected FMDV carrier cattle. The present investigation consists of a detailed analysis of the virus populations in these samples including identification and characterization of additional interserotypic minority recombinants. In every animal in which recombination was detected, recombinant viruses were identified in the OPF at the earliest sampling point after superinfection. Some recombinants remained dominant until the end of the experiment, whereas others were outcompeted by parental strains. Genomic analysis of detected recombinants suggests host immune pressure as a major driver of recombinant emergence as all recombinants had capsid-coding regions derived from the superinfecting virus to which the animals did not have detectable antibodies at the time of infection. In vitro analysis of a plaque-purified recombinant virus demonstrated a growth rate comparable to its parental precursors, and measurement of its specific infectivity suggested that the recombinant virus incurred no penalty in packaging its new chimeric genome. These findings have important implications for the potential role of persistently infected carriers in FMDV ecology and the emergence of novel strains.
| S-EPMC9231328 | biostudies-literature
Project description:Foot-and-mouth disease (FMD) field studies have suggested the occurrence of simultaneous infection of individual hosts by multiple virus strains; however, the pathogenesis of foot-and-mouth disease virus (FMDV) coinfections is largely unknown. In the current study, cattle were experimentally exposed to two FMDV strains of different serotypes (O and A). One cohort was simultaneously infected with both viruses, while additional cohorts were initially infected with FMDV A and subsequently superinfected with FMDV O after 21 or 35 days. Coinfections were confirmed during acute infection, with both viruses concurrently detected in blood, lesions, and secretions. Staggered exposures resulted in overlapping infections as convalescent animals with persistent subclinical FMDV infection were superinfected with a heterologous virus. Staggering virus exposure by 21 days conferred clinical protection in six of eight cattle, which were subclinically infected following the heterologous virus exposure. This effect was transient, as all animals superinfected at 35 days post-initial infection developed fulminant FMD. The majority of cattle maintained persistent infection with one of the two viruses while clearing the other. Analysis of viral genomes confirmed interserotypic recombination events within 10 days in the upper respiratory tract of five superinfected animals from which the dominant genomes contained the capsid coding regions of the O virus and nonstructural coding regions of the A virus. In contrast, there were no dominant recombinant genomes detected in samples from simultaneously coinfected cattle. These findings inculpate persistently infected carriers as potential FMDV mixing vessels in which novel strains may rapidly emerge through superinfection and recombination. IMPORTANCE Foot-and-mouth disease (FMD) is a viral infection of livestock of critical socioeconomic importance. Field studies from areas of endemic FMD suggest that animals can be simultaneously infected by more than one distinct variant of FMD virus (FMDV), potentially resulting in emergence of novel viral strains through recombination. However, there has been limited investigation of the mechanisms of in vivo FMDV coinfections under controlled experimental conditions. Our findings confirmed that cattle could be simultaneously infected by two distinct serotypes of FMDV, with different outcomes associated with the timing of exposure to the two different viruses. Additionally, dominant interserotypic recombinant FMDVs were discovered in multiple samples from the upper respiratory tracts of five superinfected animals, emphasizing the potential importance of persistently infected FMDV carriers as sources of novel FMDV strains.
| S-EPMC8610595 | biostudies-literature
Project description:The vaccination of the susceptible animal population against FMDV remains the most important measure to control the virus and prevent economic loss. Occurrence of infection in vaccinated animals is well-known in some diseases and is termed as breakthrough infection. The reasons include host genetic factors which can play an important role resulting in differences in susceptibility of animals to virus infection even with vaccine induced protective immune response. The Major Histocompatibility Complex (MHC) of bovines i.e. Bovine Leukocyte Antigen (BoLA) is important for antigen presentation. The BoLA DRB3 allele, which codes for the beta chain in Class II antigen, has been extensively studied and numerous reports have previously shown association of polymorphism in the gene with resistance/ susceptibility to several bacterial and viral diseases. In addition, previous studies have shown relationship between BoLA Class I and resistance or susceptibility to different diseases in cattle. The present study investigated the polymorphism in BoLA DRB3 and BoLA gene sequences of host and their relation with breakthrough FMDV infection in vaccinated animals. The study has identified three polymorphic sites each in both the genes which correlate with evidence of recent infection indicating their role in determining susceptibility of vaccinated animals to FMDV infection. Our limited study was performed on a relatively small samples size collected from one region of country. Further validation would require more detailed investigations on larger sample size.Supplementary informationThe online version contains supplementary material available at 10.1007/s13337-021-00754-8.
| S-EPMC9005608 | biostudies-literature
Project description:Profiling of miRNA in serum of FMDV infected cattle, to understand disease pathogenesis and to identify FMD specific miRNA biomarkers to aid early pre-clinical diagnosis
2017-10-20 | GSE77489 | GEO