RESUMO
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.
Assuntos
Portador Sadio/veterinária , Coinfecção/veterinária , Coinfecção/virologia , Vírus da Febre Aftosa/patogenicidade , Febre Aftosa/virologia , Infecção Persistente/veterinária , Animais , Anticorpos Antivirais/sangue , Portador Sadio/virologia , Bovinos , Doenças dos Bovinos/virologia , Vírus da Febre Aftosa/genética , Gado/virologia , Infecção Persistente/virologia , SorogrupoRESUMO
The oligoadenylate synthetase 1 (OAS1) enzyme acts as an innate sensor of viral infection and plays a major role in the defense against a wide diversity of viruses. Polymorphisms at OAS1 have been shown to correlate with differential susceptibility to several infections of great public health significance, including hepatitis C virus, SARS coronavirus, and West Nile virus. Population genetics analyses in hominoids have revealed interesting evolutionary patterns. In Central African chimpanzee, OAS1 has evolved under long-term balancing selection, resulting in the persistence of polymorphisms since the origin of hominoids, whereas human populations have acquired and retained OAS1 alleles from Neanderthal and Denisovan origin. We decided to further investigate the evolution of OAS1 in primates by characterizing intra-specific variation in four species commonly used as models in infectious disease research: the rhesus macaque, the cynomolgus macaque, the olive baboon, and the Guinea baboon. In baboons, OAS1 harbors a very low level of variation. In contrast, OAS1 in macaques exhibits a level of polymorphism far greater than the genomic average, which is consistent with the action of balancing selection. The region of the enzyme that directly interacts with viral RNA, the RNA-binding domain, contains a number of polymorphisms likely to affect the RNA-binding affinity of OAS1. This strongly suggests that pathogen-driven balancing selection acting on the RNA-binding domain of OAS1 is maintaining variation at this locus. Interestingly, we found that a number of polymorphisms involved in RNA-binding were shared between macaques and chimpanzees. This represents an unusual case of convergent polymorphism.
Assuntos
2',5'-Oligoadenilato Sintetase/genética , Resistência à Doença/genética , Haplótipos/genética , Polimorfismo Genético/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Evolução Molecular , Macaca fascicularis/genética , Macaca fascicularis/imunologia , Macaca mulatta/genética , Macaca mulatta/imunologia , Papio anubis/genética , Papio anubis/imunologia , Papio papio/genética , Papio papio/imunologia , Estrutura Terciária de Proteína , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
Superinfection of cattle persistently infected with foot-and-mouth disease virus (FMDV), with a heterologous FMDV strain has been shown to generate novel recombinant viruses. In this study, we investigated the pathogenesis events within specific tissues associated with FMDV coinfections in cattle subjected to either simultaneous or serial exposure to two distinct strains of FMDV. Both strains of FMDV (one each of serotypes O and A) were similarly localized to the nasopharyngeal mucosa during the early stages of infection. However, while no recombinant FMDV genomes were recovered from simultaneously coinfected cattle, interserotypic recombinants were isolated from nasopharyngeal tissue samples obtained at 48 h after heterologous superinfection of a persistently infected FMDV carrier. Additionally, analysis of FMDV genomes obtained from replicate nasopharyngeal tissue samples demonstrated that adjacent segments of the mucosa were sometimes infected by distinct viruses, demonstrating a multifocal and heterogeneous distribution of FMDV infection during primary and persistent phases of infection. This work indicates that superinfection of FMDV carriers may be an important source of emergent recombinant strains of FMDV in areas where multiple strains are co-circulating. IMPORTANCE Foot-and-mouth disease (FMD) is a socioeconomically impactful livestock disease with a complex epidemiology and ecology. Although recombinant viruses have been identified in field samples, the mechanisms of emergence of those viruses have never been elucidated. This current study demonstrates how serial infection of cattle with two distinct serotypes of FMD virus (FMDV) leads to rapid generation of recombinant viruses in the upper respiratory tracts of infected animals. This finding is particularly relevant in relation to the management of persistently infected FMDV carrier cattle that can maintain subclinical FMDV infection for months to years after an initial infection. Such carrier animals may function as mixing vessels that facilitate the emergence of novel recombinant FMDV strains in areas where multiple virus strains are in circulation.
Assuntos
Coinfecção , Vírus da Febre Aftosa , Febre Aftosa , Superinfecção , Animais , Bovinos , Vírus da Febre Aftosa/genética , Coinfecção/veterinária , Recombinação GenéticaRESUMO
Codon deoptimization (CD) has been recently used as a possible strategy to derive foot-and-mouth disease (FMD) live-attenuated vaccine (LAV) candidates containing DIVA markers. However, reversion to virulence, or loss of DIVA, from possible recombination with wild-type (WT) strains has yet to be analyzed. An in vitro assay was developed to quantitate the levels of recombination between WT and a prospective A24-P2P3 partially deoptimized LAV candidate. By using two genetically engineered non-infectious RNA templates, we demonstrate that recombination can occur within non-deoptimized viral genomic regions (i.e., 3'end of P3 region). The sequencing of single plaque recombinants revealed a variety of genome compositions, including full-length WT sequences at the consensus level and deoptimized sequences at the sub-consensus/consensus level within the 3'end of the P3 region. Notably, after further passage, two recombinants that contained deoptimized sequences evolved to WT. Overall, recombinants featuring large stretches of CD or DIVA markers were less fit than WT viruses. Our results indicate that the developed assay is a powerful tool to evaluate the recombination of FMDV genomes in vitro and should contribute to the improved design of FMDV codon deoptimized LAV candidates.
Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Vacinas Virais , Animais , Estudos Prospectivos , Vacinas Virais/genética , Códon , Febre Aftosa/genética , Recombinação Genética , Vírus da Febre Aftosa/genéticaRESUMO
Here, we report the genome of bovine viral diarrhea virus 1 (BVDV-1) contaminating a continuous fetal bovine kidney cell line. The cell line (LFBK-αVß6) is used for the rapid isolation and serotyping of foot-and-mouth disease virus (FMDV). The sequence contains the full polyprotein-coding sequence and partial untranslated regions (UTRs).
RESUMO
We report the near-full-genome sequences of 49 isolates of serotype Asia-1 foot-and-mouth disease virus obtained from subclinically infected Asian buffalo in Islamabad Capital Region, Pakistan, in 2011 to 2012. Sequences from subclinically infected animals are exceedingly rare and complement the more commonly available sequences acquired from clinical cases.
RESUMO
We report the near-full-length genome sequences of 22 isolates of foot-and-mouth disease virus (FMDV) serotype Asia-1, lineage Sindh-08, obtained from foot-and-mouth disease outbreaks in Pakistan between 2011 and 2012. The scarcity of full-length FMDV sequences from this region enhances the importance of these new genomes for understanding the regional molecular epidemiology.
RESUMO
We report the near full genome sequences of 18 isolates of foot-and-mouth disease virus serotype O and 6 isolates of serotype A obtained from outbreaks in Pakistan between 2011 and 2012. The scarcity of full-length FMDV sequences from this region enhances the importance of these genomes for understanding regional molecular epidemiology.
RESUMO
We report the nearly full genome sequences of 14 isolates of serotype A foot-and-mouth disease virus and 5 isolates of serotype O, which were obtained from subclinically infected Asian buffalo in Pakistan in 2011 to 2012. Sequences from subclinically infected animals are rare and complement the more commonly available sequences from clinical cases.
RESUMO
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.
RESUMO
We report the genome sequences of 12 recombinant foot-and-mouth disease virus isolates from Vietnam. The recombinant strain has a capsid region from an A/Sea-97 strain and a nonstructural segment from an O/ME-SA/PanAsia strain. The isolates were obtained from two outbreak samples collected in June 2017 and 10 subclinical samples collected between 2017 and 2019.
RESUMO
Foot-and-mouth disease virus (FMDV) infects hosts as a population of closely related viruses referred to as a quasispecies. The behavior of this quasispecies has not been described in detail in natural host species. In this study, virus samples collected from vaccinated and non-vaccinated cattle up to 35 days post-experimental infection with FMDV A24-Cruzeiro were analyzed by deep-sequencing. Vaccination induced significant differences compared to viruses from non-vaccinated cattle in substitution rates, entropy, and evidence for adaptation. Genomic variation detected during early infection reflected the diversity inherited from the source virus (inoculum), whereas by 12 days post infection, dominant viruses were defined by newly acquired mutations. Mutations conferring recognized fitness gain occurred and were associated with selective sweeps. Persistent infections always included multiple FMDV subpopulations, suggesting distinct foci of infection within the nasopharyngeal mucosa. Subclinical infection in vaccinated cattle included very early bottlenecks associated with reduced diversity within virus populations. Viruses from both animal cohorts contained putative antigenic escape mutations. However, these mutations occurred during later stages of infection, at which time transmission is less likely to occur. This study improves upon previously published work by analyzing deep sequences of samples, allowing for detailed characterization of FMDV populations over time within multiple hosts.
RESUMO
Continuous surveillance for foot-and-mouth disease (FMD) in endemic settings such as West Africa is imperative to support improved local and regional control plans, with the long-term goal of regional eradication. This paper describes the genetic characterization of FMD viruses (FMDV) obtained from outbreaks in Nigeria (n = 45) and Cameroon (n = 15) during 2016 and from archival samples (n = 3) retrieved from a 2014 outbreak in Nigeria. These viruses were analysed in the context of previously published FMDV sequences from the region. Four FMDV serotypes: O, A, SAT1 and SAT2, were detected. Phylogenetic analyses of the VP1 coding sequences indicate the continuity of FMDV serotype O East Africa-3 (O/EA-3), serotype A AFRICA genotype G-IV (A/AFRICA/G-IV) and serotype South African Territories (SAT) 2 lineage VII (SAT2/VII). The FMDV SAT1 topotype X (SAT1/X), which emerged in Nigeria in 2015, continued to be associated with outbreaks in the region during 2016, and SAT1 is reported for the first time from Cameroon. Additionally, a re-emergence or re-introduction of the serotype O West Africa (O/WA) topotype in Nigeria is described herein. Our findings indicate a consistent, pan-serotypic relationship between FMDV strains detected in Cameroon and Nigeria. Additionally, FMDV strains from West Africa obtained in this study were genetically related to those occurring in East and North Africa. These phylogenetic relationships suggest that animal movements (pastoralism and/or trade) are important factors for virus spread across the African continent. These data provide critical baselines which are a necessary component of Stages 0 and 1 of the Progressive Control Pathway of FMD (PCP-FMD). Specifically, characterizing the existing virus strains (risk) provides the basis for the comprehensive risk-based control plan which is the requisite criteria for Nigeria's transition to Stage 2 of PCP-FMD, and for coordinated regional control of FMD.
Assuntos
Vírus da Febre Aftosa/genética , Febre Aftosa/virologia , Animais , Camarões/epidemiologia , Surtos de Doenças , Febre Aftosa/epidemiologia , Genótipo , Gado , Nigéria/epidemiologia , Filogenia , Vigilância da População , SorogrupoRESUMO
We report the genome sequences of seven foot-and-mouth disease (FMD) virus (FMDV) isolates collected in India between 1997 and 2009. The strains represented four sublineages within the O/ME-SA/Ind2001 lineage. These viruses provide insights into FMDV diversity and evolution in India and may influence future control measures, including vaccine selections.
RESUMO
We report a near-full-length genome sequence of a foot-and-mouth disease virus (FMDV) of serotype Southern African Territories 2 (SAT 2), topotype VII, isolated from cattle during an FMDV outbreak in Bauchi State, Nigeria, in October 2014. This provides the first SAT 2 near-full-length genome sequence from West Africa and contributes to our understanding of viral spread and evolution.
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This is the first report of two near-complete genome sequences of foot-and-mouth disease virus (FMDV) serotype O from Kenya. The viruses were isolated from bovine epithelium collected in 2014 and 2016 from local FMD outbreaks. These full-genome sequences are critical for improving the understanding of regional FMDV molecular epidemiology.
RESUMO
Foot-and-mouth disease (FMD) is a highly contagious viral disease that severely impacts global food security and is one of the greatest constraints on international trade of animal products. Extensive viral population diversity and rapid, continuous mutation of circulating FMD viruses (FMDVs) pose significant obstacles to the control and ultimate eradication of this important transboundary pathogen. The current study investigated mechanisms contributing to within-host evolution of FMDV in a natural host species (cattle). Specifically, vaccinated and non-vaccinated cattle were infected with FMDV under controlled, experimental conditions and subsequently sampled for up to 35 days to monitor viral genomic changes as related to phases of disease and experimental cohorts. Consensus-level genomic changes across the entire FMDV coding region were characterized through three previously defined stages of infection: early, transitional, and persistent. The overall conclusion was that viral evolution occurred via a combination of two mechanisms: emergence of full-genomic minority haplotypes from within the inoculum super-swarm, and concurrent continuous point mutations. Phylogenetic analysis indicated that individuals were infected with multiple distinct haplogroups that were pre-existent within the ancestral inoculum used to infect all animals. Multiple shifts of dominant viral haplotype took place during the early and transitional phases of infection, whereas few shifts occurred during persistent infection. Overall, this work suggests that the establishment of the carrier state is not associated with specific viral genomic characteristics. These insights into FMDV population dynamics have important implications for virus sampling methodology and molecular epidemiology.
Assuntos
Portador Sadio/veterinária , Evolução Molecular , Vírus da Febre Aftosa/genética , Febre Aftosa/virologia , Genoma Viral/genética , Animais , Proteínas do Capsídeo/genética , Portador Sadio/imunologia , Portador Sadio/virologia , Bovinos , Doenças dos Bovinos/imunologia , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/virologia , Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Vírus da Febre Aftosa/imunologia , Vírus da Febre Aftosa/isolamento & purificação , Haplótipos , Estudos Longitudinais , Mutação , Filogenia , RNA Viral/genética , Vacinas Virais/administração & dosagemRESUMO
We report the full polyprotein-coding sequences and partial untranslated regions (UTRs) of 18 foot-and-mouth disease (FMD) viruses from 4 outbreaks in India in 2013 and 2014. All strains grouped within the O/ME-SA/Ind2001d sublineage. These genomes update knowledge of FMD virus (FMDV) diversity in South Asia and may contribute to molecular epidemiology studies and vaccine selections.
RESUMO
In 2018, senecavirus A was detected for the first time in Vietnam. This report contains the first complete genome of a senecavirus A isolate collected from pigs in Kon Tum Province, Vietnam. This novel incursion has substantial implications for regional control of vesicular transboundary diseases.
RESUMO
We report the polyprotein coding sequence of the newly defined Ind2001e sublineage of foot-and-mouth disease virus (FMDV) serotype O, isolated from a bovine epithelial tissue sample collected in 2017 in Kon Tum Province, Vietnam. This discovery updates FMDV diversity in Vietnam, has implications for FMDV epidemiology, and influences future vaccine selections.