RESUMEN
Hospital-based and community-based 'high-risk cohort' studies investigating humans at risk of zoonotic infection due to occupational or residential exposure to animals were conducted in Vietnam, with diverse viruses identified from faecal samples collected from humans, domestic and wild animals. In this study, we focus on the positive-sense RNA virus family Picornaviridae, investigating the prevalence, diversity, and potential for cross-species transmission. Through metagenomic sequencing, we found picornavirus contigs in 23% of samples, belonging to 15 picornavirus genera. Prevalence was highest in bats (67%) while diversity was highest in rats (nine genera). In addition, 22% of the contigs were derived from novel viruses: Twelve phylogenetically distinct clusters were observed in rats of which seven belong to novel species or types in the genera Hunnivirus, Parechovirus, Cardiovirus, Mosavirus and Mupivirus; four distinct clusters were found in bats, belonging to one novel parechovirus species and one related to an unclassified picornavirus. There was no evidence for zoonotic transmission in our data. Our study provides an improved knowledge of the diversity and prevalence of picornaviruses, including a variety of novel picornaviruses in rats and bats. We highlight the importance of monitoring the human-animal interface for possible spill-over events.
Asunto(s)
Variación Genética , Genoma Viral , Infecciones por Picornaviridae/epidemiología , Infecciones por Picornaviridae/transmisión , Picornaviridae/genética , Animales , Quirópteros/virología , Estudios de Cohortes , Heces/virología , Humanos , Metagenómica , Filogenia , Picornaviridae/clasificación , Picornaviridae/patogenicidad , Infecciones por Picornaviridae/veterinaria , Infecciones por Picornaviridae/virología , Prevalencia , ARN Viral/genética , Ratas/virología , Vietnam/epidemiologíaRESUMEN
Senecavirus A (SVA) is a picornavirus that circulates in swine populations worldwide causing vesicular disease (VD) in affected animals. Here we developed a reverse genetics system for SVA based on the well-characterized wild-type SVA strain SD15-26 (wt SVA SD15-26). The full-length cDNA genome of SVA was cloned into a plasmid under a T7 RNA polymerase promoter. Following in vitro transcription, the genomic viral RNA was transfected into BHK-21 cells and rescue of infectious virus (rSVA SD15-26) was shown by inoculation of highly susceptible H1299 cells. In vitro characterization of the rSVA SD15-26 showed similar replication properties and protein expression levels as the wt SVA SD15-26. A pathogenesis study was conducted in 15-week-old finishing pigs to evaluate the pathogenicity and infection dynamics of the rSVA SD15-26 virus in comparison to the wt SVA SD15-26. Animals from both rSVA- and wt SVA SD15-26-inoculated groups presented characteristic SVA clinical signs (lethargy and lameness) followed by the development of vesicular lesions on the snout and/or feet. The clinical outcome of infection, including disease onset, severity and duration was similar in rSVA- and the wt SVA SD15-26-inoculated animals. All animals inoculated with rSVA or with wt SVA SD15-26 presented a short-term viremia, and animals from both groups shed similar amounts of virus in oral and nasal secretion, and faeces. Our data demonstrates that the rSVA SD5-26 clone is fully virulent and pathogenic in pigs, presenting comparable pathogenesis and infection dynamics to the wt SVA SD15-26 strain. The infectious clone generated here is a useful platform to study virulence determinants of SVA, and to dissect other aspects of SVA infection biology, pathogenesis and persistence.
Asunto(s)
Infecciones por Picornaviridae , Picornaviridae/patogenicidad , Enfermedades de los Porcinos/virología , Animales , Línea Celular , Cricetinae , Humanos , Infecciones por Picornaviridae/veterinaria , Infecciones por Picornaviridae/virología , Porcinos , Viremia/virología , VirulenciaRESUMEN
BACKGROUND: Data on the neurodevelopment of children who experienced central nervous system (CNS) infections with enteroviruses (EV) or parechoviruses (hPeV) is scarce and mostly limited to follow up of short-term outcomes. METHODS: Parents of children who presented between 2014 and 2019, underwent a lumbar puncture and whose cerebrospinal fluid was polymerase chain reaction positive for EV or hPeV, were asked to complete a care-giver-administered neurodevelopmental assessment tool (The Ages and Stages Instrument [ASQ3]). Clinical data of the infective episode were collected from patient notes. RESULTS: Of 101 children, 43 (10 hPeV+, 33 EV+) submitted ASQ3 results. Median age at assessment was 38.9 months (interquartile range, 15.4-54.8), the follow-up interval 3 years (median 37 months; interquartile range, 13.9-53.1). Age, inflammatory markers, and cerebrospinal fluid pleocytosis during the infective event were not associated with ASQ3 scores. In 23 children (17 EV+, 6 hPeV+), no neurodevelopmental concerns were reported. Two more had preexisting developmental delay and were excluded. Of the remaining, 18/41 (43.9%) reported ASQ3 scores indicating need for monitoring or professional review in at least 1 category, not differing by pathogen (EV 14/31, 45.2%; hPeV 4/10, 40%; P = 0.71). Seven children will require formal review, scoring ≥2 SD below the mean in at least 1 category (6/31 EV+, 1/10 hPeV+, P = 0.7), 3 scored ≥2 SD below the mean in more than 1 area. CONCLUSIONS: Parent-administered developmental assessment of children with a history of early picornavirus infection of the CNS identified a subgroup that requires formal neurodevelopmental review. Wider application of community-based developmental screening will complement our understanding of the impact of CNS infections in early childhood.
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Infecciones del Sistema Nervioso Central/complicaciones , Infecciones del Sistema Nervioso Central/virología , Trastornos del Neurodesarrollo/diagnóstico , Trastornos del Neurodesarrollo/etiología , Padres , Infecciones por Picornaviridae/complicaciones , Picornaviridae/genética , Niño , Preescolar , Enterovirus/genética , Estudios de Seguimiento , Humanos , Lactante , Tamizaje Masivo/métodos , Trastornos del Neurodesarrollo/virología , Parechovirus/genética , Picornaviridae/patogenicidad , Infecciones por Picornaviridae/líquido cefalorraquídeo , Encuestas y CuestionariosRESUMEN
Among enteric viruses, rotavirus A (RVA), norovirus (NoV), adenovirus, and astrovirus (AstV) are the major etiological agents associated in acute gastroenteritis. The present study highlights, clinical, epidemiological, and molecular aspects with respect to RVA, NoV, enterovirus (EV), and human parechovirus (HPeVs) in sporadic cases (n = 305) of acute gastroenteritis, Pune (Maharashtra), Western India. Detection of RVA was carried out by enzyme-linked immunosorbent assay, NoV, EV, and HPeVs by reverse transcription PCR. Prevalence of 36.06%, 20.32%, 14.09%, 3.93%, respectively was observed for RVA, EV, HPeVs, and NoV along with coinfections. Infections occurred in children less than 2 years old, with peak infections within 12 months age. The disease severity in RV infections was found high (70.90%) with severe disease, followed by EV (62.9%), NoV (58.33%), and HPeV (44.58%). Predominant strains of RV G1P[8], G2P[4] types with unusual G9P[4], NoV Genogroup II of genotype 4 strains and multiple EV types with EV-B species, E14 and E17 and two novel EV-75, EV-107 types were detected. Circulation of heterogeneous HPeV genotypes (HPeV1-5, 7, 8, 13, 14, 16) with predominance of HPeV-1 was noticed. Changing trends in circulation of a rare HPeV-2 genotype, with emerging and reemerging strains was noted. The study highlights association of RVA, NoV, EV, and HPeV and their mono-infections, genotype distribution, and changing trends in acute gastroenteritis, and added more knowledge on rota and nonrota enteric viruses in acute gastroenteritis. More such studies in rota vaccinated era are required across the country, as Indian rotavirus vaccine has been implemented under the National Immunization program.
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Gastroenteritis/epidemiología , Genotipo , Filogenia , Infecciones por Picornaviridae/epidemiología , Picornaviridae/clasificación , Picornaviridae/genética , Antígenos Virales/genética , Proteínas de la Cápside/genética , Preescolar , Heces/virología , Gastroenteritis/virología , Variación Genética , Humanos , India/epidemiología , Lactante , Recién Nacido , Picornaviridae/patogenicidad , Infecciones por Picornaviridae/virología , Estudios Retrospectivos , Análisis de Secuencia de ADNRESUMEN
Senecavirus A (SVA) was discovered as a cell culture contaminant in 2002, and multiple attempts to experimentally reproduce disease were unsuccessful. Field reports of porcine idiopathic vesicular disease (PIVD) cases testing PCR positive for SVA in addition to outbreaks of PIVD in Brazil and the United States in 2015 suggested SVA was a causative agent, which has now been consistently demonstrated experimentally. Ease of experimental reproduction of disease with contemporary strains of SVA raised questions concerning the difficulty of reproducing vesicular disease with historical isolates. The following study was conducted to compare the pathogenicity of SVA between historical and contemporary isolates in growing pigs. Six groups of pigs (n = 8) were intranasally inoculated with the following SVA isolates: SVV001/2002, CAN/2011, HI/2012, IA/2015, NC/2015, SD/2015. All isolates induced vesicular disease in at least half of the inoculated pigs from each group. All pigs replicated virus as demonstrated by serum and/or swab samples positive for SVA by quantitative PCR. Pig sera tested by virus neutralization assay demonstrated cross-neutralizing antibodies against all viruses utilized in the study. Cross-neutralizing antibodies from pigs inoculated with historical isolates were lower than those pigs that were inoculated with contemporary isolates. Phylogenetic analysis revealed two clades with SVV001/2002 being in a separate clade compared to the other five isolates. Although differences in the infection kinetics and sequences of these six isolates were found, clinical presentation of vesicular disease was similar between both historical and contemporary isolates.
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Anticuerpos Neutralizantes/sangre , Infecciones por Picornaviridae/veterinaria , Picornaviridae/genética , Picornaviridae/aislamiento & purificación , Enfermedades de los Porcinos/virología , Animales , Anticuerpos Antivirales/sangre , Brasil/epidemiología , Línea Celular , Brotes de Enfermedades , Genoma Viral , Historia del Siglo XX , Historia del Siglo XXI , Masculino , Filogenia , Picornaviridae/clasificación , Picornaviridae/patogenicidad , Infecciones por Picornaviridae/epidemiología , Infecciones por Picornaviridae/historia , Porcinos , Enfermedades de los Porcinos/epidemiología , Enfermedades de los Porcinos/historia , Estados Unidos/epidemiologíaRESUMEN
Sporadic outbreaks of Seneca Valley virus (SVV) have been detected in recent years causing huge economic losses to the pig industry. SVV infection can lead to redness and fever of the mouth, nose or hoof wall, ulcerative injury and inflammation in pigs. Although long non-coding RNAs (lncRNAs) have been shown to play an important role in antiviral and inflammatory regulation, how lncRNAs regulate and induce SVV infection inflammation remains unclear. Here, we found the differential expression of 1332 lncRNAs and 3299 mRNAs in SVV-infected ST cells using RNA-seq. Functional annotation analysis revealed that regulated transcripts are mainly involved in signaling pathways related to host immunity and inflammatory responses. We identified lnc-MSTRG.18940.1 as an important immune regulator in SVV infection. Lnc-MSTRG.18940.1 silencing specifically inhibited SVV replication and the production of inflammatory factors TNF-α, IL-1, IL-6, and IL-8. Our findings aid to a better understanding of host responses to SVV infection and provide new directions for understanding the potential association between lncRNAs and SVV pathogenesis.
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Infecciones por Picornaviridae/veterinaria , Picornaviridae/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/inmunología , Enfermedades de los Porcinos/inmunología , Animales , Línea Celular , Perfilación de la Expresión Génica , Picornaviridae/patogenicidad , Infecciones por Picornaviridae/inmunología , Infecciones por Picornaviridae/virología , RNA-Seq , Porcinos , Enfermedades de los Porcinos/virologíaRESUMEN
Picornaviruses have both asexual and sexual RNA replication mechanisms. Asexual RNA replication mechanisms involve one parental template, whereas sexual RNA replication mechanisms involve two or more parental templates. Because sexual RNA replication mechanisms counteract ribavirin-induced error catastrophe, we selected for ribavirin-resistant poliovirus to identify polymerase residues that facilitate sexual RNA replication mechanisms. We used serial passage in ribavirin, beginning with a variety of ribavirin-sensitive and ribavirin-resistant parental viruses. Ribavirin-sensitive virus contained an L420A polymerase mutation, while ribavirin-resistant virus contained a G64S polymerase mutation. A G64 codon mutation (G64Fix) was used to inhibit emergence of G64S-mediated ribavirin resistance. Revertants (L420) or pseudorevertants (L420V and L420I) were selected from all independent lineages of L420A, G64Fix L420A, and G64S L420A parental viruses. Ribavirin resistance G64S mutations were selected in two independent lineages, and novel ribavirin resistance mutations were selected in the polymerase in other lineages (M299I, M323I, M392V, and T353I). The structural orientation of M392, immediately adjacent to L420 and the polymerase primer grip region, led us to engineer additional polymerase mutations into poliovirus (M392A, M392L, M392V, K375R, and R376K). L420A revertants and pseudorevertants (L420V and L420I) restored efficient viral RNA recombination, confirming that ribavirin-induced error catastrophe coincides with defects in sexual RNA replication mechanisms. Viruses containing M392 mutations (M392A, M392L, and M392V) and primer grip mutations (K375R and R376K) exhibited divergent RNA recombination, ribavirin sensitivity, and biochemical phenotypes, consistent with changes in the fidelity of RNA synthesis. We conclude that an extended primer grip of the polymerase, including L420, M392, K375, and R376, contributes to the fidelity of RNA synthesis and to efficient sexual RNA replication mechanisms.IMPORTANCE Picornaviruses have both asexual and sexual RNA replication mechanisms. Sexual RNA replication shapes picornavirus species groups, contributes to the emergence of vaccine-derived polioviruses, and counteracts error catastrophe. Can viruses distinguish between homologous and nonhomologous partners during sexual RNA replication? We implicate an extended primer grip of the viral polymerase in sexual RNA replication mechanisms. By sensing RNA sequence complementarity near the active site, the extended primer grip of the polymerase has the potential to distinguish between homologous and nonhomologous RNA templates during sexual RNA replication.
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Picornaviridae/genética , ARN Polimerasa Dependiente del ARN/genética , Replicación Viral/efectos de los fármacos , Sustitución de Aminoácidos/genética , Antivirales/farmacología , ARN Polimerasas Dirigidas por ADN/genética , ARN Polimerasas Dirigidas por ADN/metabolismo , Farmacorresistencia Viral/efectos de los fármacos , Células HeLa , Humanos , Mutación/efectos de los fármacos , Picornaviridae/metabolismo , Picornaviridae/patogenicidad , Infecciones por Picornaviridae/genética , Infecciones por Picornaviridae/metabolismo , Poliovirus/genética , ARN/genética , ARN Viral/genética , ARN Polimerasa Dependiente del ARN/metabolismo , Ribavirina/farmacología , Replicación Viral/genéticaRESUMEN
Porcine sapelovirus (PSV) is a causative agent of acute diarrhoea, pneumonia and reproductive disorders in swine. Since PSV infection interrupts the growth of other viruses due to its high replication capability in cell culture, the prevention of PSV replication is a keystone to the isolation of non-PSV agents from PSV-contaminated samples. In the present study, we established the PSV infection-resistant cell line N1380 and isolated three mammalian orthoreoviruses (MRV) strains, sR1521, sR1677 and sR1590, from swine in Taiwan. These Taiwanese isolates induced an extensive cytopathic effect in N1380 cells upon infection. The complete and empty virus particles were purified from the cell culture supernatants. Next-generation sequencing analyses revealed that the complete virus particles contained 10 segments, including 3 large (L1, L2 and L3), 3 medium (M1, M2 and M3) and 4 small (S1, S2, S3 and S4) segments. In contrast, the empty virus particles without genome were non-infectious. Phylogenetic analyses revealed that the Taiwanese strains belong to serotype 2 MRV (MRV2). We established an ELISA for the detection of IgG antibody against MRV2 by using the empty virus particles as the antigen. A total of 540 swine and 95 wild boar serum samples were collected in Japan, and the positive rates were 100% and 52.6%, respectively. These results demonstrated that MRV infection occurred frequently in both swine and wild boar in Japan. We established a cell line that is efficient for the isolation of MRV, and the ELISA based on the naturally occurring empty particles would be of great value for the surveillance of MRV-related diseases.
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Orthoreovirus de los Mamíferos/aislamiento & purificación , Infecciones por Picornaviridae/veterinaria , Picornaviridae/patogenicidad , Infecciones por Reoviridae/veterinaria , Enfermedades de los Porcinos/virología , Animales , Anticuerpos Antivirales/sangre , Western Blotting/veterinaria , Sistemas CRISPR-Cas , Línea Celular , Electroforesis en Gel de Poliacrilamida/veterinaria , Ensayo de Inmunoadsorción Enzimática/veterinaria , Heces/virología , Secuenciación de Nucleótidos de Alto Rendimiento/veterinaria , Inmunoglobulina G/sangre , Microscopía Electrónica/veterinaria , Orthoreovirus de los Mamíferos/genética , Orthoreovirus de los Mamíferos/inmunología , Filogenia , Infecciones por Picornaviridae/virología , ARN Viral/genética , Infecciones por Reoviridae/virología , PorcinosRESUMEN
Senecavirus A (SVA), formerly known as Seneca Valley virus, is a single-strand, positive-sense RNA virus in the family Picornaviridae. This virus has been associated with recent outbreaks of vesicular disease (SVA-VD) and epidemic transient neonatal losses (ETNL) in several swine-producing countries. The clinical manifestation of and lesion caused by SVA are indistinguishable from other vesicular diseases. Pathogenicity studies indicate that SVA could regulate the host innate immune response to facilitate virus replication and the spread of the virus to bystander cells. SVA infection can induce specific humoral and cellular responses that can be detected within the first week of infection. However, SVA seems to produce persistent infection, and the virus can be shed in oral fluids for a month and detected in tissues for approximately two months after experimental infection. SVA transmission could be horizontal or vertical in infected herds of swine, while positive animals can also remain subclinical. In addition, mice seem to act as reservoirs, and the virus can persist in feed and feed ingredients, increasing the risk of introduction into naïve farms. Besides the pathological effects in swine, SVA possesses cytolytic activity, especially in neoplastic cells. Thus, SVA has been evaluated in phase II clinical trials as a virotherapy for neuroendocrine tumors. The goal of this review is summarize the current SVA-related research in pathogenesis, immunity, epidemiology and advances in diagnosis as well as discuses current challenges with subclinical/persistent presentation.
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Infecciones por Picornaviridae/epidemiología , Infecciones por Picornaviridae/veterinaria , Picornaviridae/inmunología , Picornaviridae/patogenicidad , Enfermedades de los Porcinos/diagnóstico , Enfermedades de los Porcinos/epidemiología , Animales , Brotes de Enfermedades , Ratones , Infecciones por Picornaviridae/diagnóstico , Porcinos , Enfermedades de los Porcinos/virologíaRESUMEN
Senecavirus A (SVA), previously called Seneca Valley virus, can cause vesicular lesions in sows and a sharp decline in neonatal piglet production. In this study, a SVA strain was isolated from a pig herd in Shandong Province in China and identified as SVV-CH-SD. The full genome was 7286 nucleotides (nt) in length and contained a single open reading frame (ORF) of 6546 nt, encoding a 2182 amino acid (aa). A phylogenetic analysis showed that the isolate shares highest sequence homology (98.52 %) with SVA strain USA-GBI26-2015. A genetic comparison of virulent and weakly virulent SVA strains showed that some amino acid residues may be associated with virulence. Animal challenge experiments showed that 90-100-day-old pigs inoculated with SVV-CH-SD intraorally and intranasally, intranasally, or intramuscularly developed low fever, blisters, and lameness. They had similar levels of neutralizing antibodies against SVA and viral loads in the serum and organs at 28 days post-CHallenge. However, 30-35- and 55-65-day-old pigs challenged with SVV-CH-SD showed no clinical signs, although anti-SVA neutralizing antibodies were detected. Our findings provide useful data for studying the pathogenesis and transmission of SVA in pigs.
Asunto(s)
Genoma Viral , Infecciones por Picornaviridae/veterinaria , Picornaviridae/genética , Picornaviridae/patogenicidad , Enfermedades de los Porcinos/virología , Porcinos/virología , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , China , Femenino , Masculino , Filogenia , Picornaviridae/aislamiento & purificación , Infecciones por Picornaviridae/transmisión , Infecciones por Picornaviridae/virología , Enfermedades de los Porcinos/transmisión , Carga Viral , Virulencia , Secuenciación Completa del GenomaRESUMEN
BACKGROUND: Initially, detection and isolation of Aichivirus as a new member of Picornaviridae family was documented in Japan. Aichivirus species belongs to genus Kobuvirus, including 3 genotypes A, B and C. In previous studies, it has been suggested that Aichivirus infect humans by fecal-oral route. To establish an investigation for the occurrence of Aichivirus among pediatric patients involved to acute gastroenteritis, we developed a reverse transcription quantitative polymerase chain reaction assay for detection and quantification of Aichivirus in stool specimens. MATERIAL AND METHODS: In this study, a total of 160 stool samples from September 2018 to May 2019 were collected from pediatric patients presenting with acute gastroenteritis in Karaj hospital, Iran. After viral RNA extraction, the reverse transcription quantitative polymerase chain reaction was performed to amplify the 3CD junction region of Aichivirus genome and viral load was assessed. Aichivirus genomic RNA was detected in 13/160 (8.1%) of stool samples. The highest Aichivirus detection rate was in December (30.7%). The maximum viral load was determined to be 3.9 × 10 copies/g in one sample obtained from a 1-month-old patient. The co-infection of Aichivirus with salivirus and saffold virus was also assessed by reverse transcription quantitative polymerase chain reaction, among which frequent mixed infections by 2 or more viruses were identified. CONCLUSIONS: This is the first documentation of Aichivirus detection in stool samples that demonstrates Aichivirus has been circulating among Iranian pediatric patients.
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Gastroenteritis/epidemiología , Infecciones por Picornaviridae/epidemiología , Picornaviridae/genética , Enfermedad Aguda/epidemiología , Niño , Preescolar , Diarrea/epidemiología , Diarrea/virología , Heces/virología , Femenino , Gastroenteritis/virología , Genoma Viral , Humanos , Lactante , Irán/epidemiología , Masculino , Filogenia , Picornaviridae/clasificación , Picornaviridae/patogenicidad , ARN Viral/genética , Estudios Retrospectivos , Carga ViralRESUMEN
This Invited Review is a kind of scientific autobiography based on the presentation at the Symposium "Viruses: Discovering Big in Small" held in honor of the author's 90th birthday (Moscow, March 2019).
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Investigación Biomédica/historia , Infecciones por Picornaviridae/virología , Picornaviridae/fisiología , Picornaviridae/patogenicidad , Transporte Activo de Núcleo Celular , Apoptosis , Investigación Biomédica/educación , Evolución Molecular , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Picornaviridae/genética , Picornaviridae/metabolismo , Infecciones por Picornaviridae/epidemiología , Infecciones por Picornaviridae/metabolismo , Infecciones por Picornaviridae/prevención & control , ARN Viral/biosíntesis , ARN Viral/genética , Proteínas Virales/genética , Proteínas Virales/metabolismo , Replicación ViralRESUMEN
The objective of this study was to investigate whether a virulent Canadian isolate of Senecavirus A (SVA) causes idiopathic vesicular disease (IVD) in pigs. Senecavirus A, which was first isolated in the United States in 2002 as Seneca Valley Virus, was linked to cases of porcine idiopathic vesicular disease in Canada in 2007 and in the United States in 2010. Since 2014, SVA outbreaks in Brazil, the US, Canada, China, Thailand, and Colombia point to an expanding global distribution and the need to study the pathogenicity of the virus. Unlike the prototype virus, recent US isolates of SVA have been shown to cause vesicular disease in pigs. We report vesicular disease in pigs following experimental inoculation with a 2016 Canadian isolate of SVA. All inoculated pigs developed vesicular lesions regardless of route of inoculation. Virus was detected in blood and oral fluids as well as on oral and fecal swabs. In addition, all pigs seroconverted to SVA by 6 days post-inoculation (DPI). This study confirms that recent Canadian isolates of SVA cause vesicular disease in pigs and highlights the importance of monitoring SVA for increased virulence.
L'objectif de la présente étude était d'examiner si un isolat canadien virulent de Senecavirus A (SVA) causait une maladie vésiculaire idiopathique (IVD) chez les porcs. Le SVA, qui fut isolé pour la première fois aux États-Unis en 2002 comme le virus de la vallée de Seneca, a été associé à des cas d'IVD porcine au Canada en 2007 et aux États-Unis en 2010. Depuis 2014, des épidémies de SVA au Brésil, aux États-Unis, au Canada, en Chine, en Thaïlande, et en Colombie indiquent une distribution globale en expansion et un besoin d'étudier la pathogénicité du virus. Contrairement au prototype du virus, des isolats récents de SVA aux États-Unis ont été démontrés comme causant une maladie vésiculaire chez les porcs. Nous rapportons ici une maladie vésiculaire chez des porcs à la suite de l'inoculation expérimentale d'un isolat canadien de SVA obtenu en 2016.Tous les porcs inoculés ont développé des lésions vésiculaires indépendamment de la voie d'inoculation. Le virus fut détecté dans le sang et les fluides oraux ainsi qu'à partir d'écouvillons oral et fécal. De plus, tous les porcs ont séro-convertis au SVA au 6e jour post-inoculation. Cette étude confirme que des isolats canadiens récents de SVA causent une maladie vésiculaire chez les porcs et souligne l'importance de surveiller l'augmentation de virulence du SVA.(Traduit par Docteur Serge Messier).
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Infecciones por Picornaviridae/veterinaria , Picornaviridae/patogenicidad , Enfermedades de los Porcinos/virología , Animales , Anticuerpos Antivirales/sangre , Canadá/epidemiología , Ensayo de Inmunoadsorción Enzimática , Pruebas de Neutralización , Infecciones por Picornaviridae/epidemiología , Infecciones por Picornaviridae/patología , Infecciones por Picornaviridae/virología , Porcinos , Enfermedades de los Porcinos/patología , VirulenciaRESUMEN
Accumulating evidence suggests that intestinal bacteria promote enteric virus infection in mice. For example, previous work demonstrated that antibiotic treatment of mice prior to oral infection with poliovirus reduced viral replication and pathogenesis. Here, we examined the effect of antibiotic treatment on infection with coxsackievirus B3 (CVB3), a picornavirus closely related to poliovirus. We treated mice with a mixture of five antibiotics to deplete host microbiota and examined CVB3 replication and pathogenesis following oral inoculation. We found that, as seen with poliovirus, CVB3 shedding and pathogenesis were reduced in antibiotic-treated mice. While treatment with just two antibiotics, vancomycin and ampicillin, was sufficient to reduce CVB3 replication and pathogenesis, this treatment had no effect on poliovirus. The quantity and composition of bacterial communities were altered by treatment with the five-antibiotic cocktail and by treatment with vancomycin and ampicillin. To determine whether more-subtle changes in bacterial populations impact viral replication, we examined viral infection in mice treated with milder antibiotic regimens. Mice treated with one-tenth the standard concentration of the normal antibiotic cocktail supported replication of poliovirus but not CVB3. Importantly, a single dose of one antibiotic, streptomycin, was sufficient to reduce CVB3 shedding and pathogenesis while having no effect on poliovirus shedding and pathogenesis. Overall, replication and pathogenesis of CVB3 are more sensitive to antibiotic treatment than poliovirus, indicating that closely related viruses may differ with respect to their reliance on microbiota.IMPORTANCE Recent data indicate that intestinal bacteria promote intestinal infection of several enteric viruses. Here, we show that coxsackievirus, an enteric virus in the picornavirus family, also relies on microbiota for intestinal replication and pathogenesis. Relatively minor depletion of the microbiota was sufficient to decrease coxsackievirus infection, while poliovirus infection was unaffected. Surprisingly, a single dose of one antibiotic was sufficient to reduce coxsackievirus infection. Therefore, these data indicate that closely related viruses may differ with respect to their reliance on microbiota.
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Infecciones por Enterovirus/microbiología , Infecciones por Enterovirus/virología , Enterovirus/efectos de los fármacos , Enterovirus/patogenicidad , Microbiota/efectos de los fármacos , Ampicilina/farmacología , Animales , Antibacterianos/farmacología , Bacterias/clasificación , Infecciones por Coxsackievirus , Modelos Animales de Enfermedad , Células HeLa , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Picornaviridae/efectos de los fármacos , Picornaviridae/patogenicidad , Poliovirus/efectos de los fármacos , Poliovirus/patogenicidad , Vancomicina/farmacología , Replicación Viral/efectos de los fármacosRESUMEN
The picornavirus family includes poliovirus (PV) (genus: enterovirus), human rhinoviruses (enterovirus) and foot-and-mouth disease virus (FMDV) (aphthovirus). These are responsible for important human and animal health concerns worldwide including poliomyelitis, the common cold and foot-and-mouth disease (FMD) respectively. In picornavirus particles, the positive-sense RNA genome (ca. 7-9 kb) is packaged within a protein shell (capsid) usually consisting of three surface exposed proteins, VP1, VP2 and VP3 plus the internal VP4, which are generated following cleavage of the capsid precursor by a virus-encoded protease. We have previously identified a motif near the C-terminus of FMDV VP1 that is required for capsid precursor processing. This motif is highly conserved among other picornaviruses, and is also likely to be important for their capsid precursor processing. We have now determined the plasticity of residues within this motif for virus infectivity and found an important interaction between FMDV residue VP1 R188 within this conserved motif and residue W129 in VP2 that is adjacent in the virus capsid. The FMDV (VP1 R188A) mutant virus has only been rescued with the secondary substitution VP2 W129R. This additional change compensates for the defect resulting from the VP1 R188A substitution and restored both capsid precursor processing and virus viability.
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Cápside/metabolismo , Picornaviridae/patogenicidad , Secuencia de Aminoácidos , Cápside/química , Secuencia Conservada , Humanos , Picornaviridae/metabolismo , VirulenciaRESUMEN
Due to the limiting coding capacity for members of the Picornaviridae family of positive-strand RNA viruses, their successful replication cycles require complex interactions with host cell functions. These interactions span from the down-modulation of many aspects of cellular metabolism to the hijacking of specific host functions used during viral translation, RNA replication, and other steps of infection by picornaviruses, such as human rhinovirus, coxsackievirus, poliovirus, foot-and-mouth disease virus, enterovirus D-68, and a wide range of other human and nonhuman viruses. Although picornaviruses replicate exclusively in the cytoplasm of infected cells, they have extensive interactions with host cell nuclei and the proteins and RNAs that normally reside in this compartment of the cell. This review will highlight some of the more recent studies that have revealed how picornavirus infections impact the RNA metabolism of the host cell posttranscriptionally and how they usurp and modify host RNA binding proteins as well as microRNAs to potentiate viral replication.
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Interacciones Huésped-Patógeno , Infecciones por Picornaviridae/virología , Picornaviridae/patogenicidad , ARN/metabolismo , Replicación Viral , Animales , Humanos , Infecciones por Picornaviridae/genética , Infecciones por Picornaviridae/metabolismo , ARN/genéticaRESUMEN
Senecavirus A (SVA) is a picornavirus that causes acute vesicular disease (VD), that is clinically indistinguishable from foot-and-mouth disease (FMD), in pigs. Notably, SVA RNA has been detected in lymphoid tissues of infected animals several weeks following resolution of the clinical disease, suggesting that the virus may persist in select host tissues. Here, we investigated the occurrence of persistent SVA infection and the contribution of stressors (transportation, immunosuppression, or parturition) to acute disease and recrudescence from persistent SVA infection. Our results show that transportation stress leads to a slight increase in disease severity following infection. During persistence, transportation, immunosuppression, and parturition stressors did not lead to overt/recrudescent clinical disease, but intermittent viremia and virus shedding were detected up to day 60 postinfection (p.i.) in all treatment groups following stress stimulation. Notably, real-time PCR and in situ hybridization (ISH) assays confirmed that the tonsil harbors SVA RNA during the persistent phase of infection. Immunofluorescence assays (IFA) specific for double-stranded RNA (dsRNA) demonstrated the presence of double-stranded viral RNA in tonsillar cells. Most importantly, infectious SVA was isolated from the tonsil of two animals on day 60 p.i., confirming the occurrence of carrier animals following SVA infection. These findings were supported by the fact that contact piglets (11/44) born to persistently infected sows were infected by SVA, demonstrating successful transmission of the virus from carrier sows to contact piglets. Results here confirm the establishment of persistent infection by SVA and demonstrate successful transmission of the virus from persistently infected animals.IMPORTANCE Persistent viral infections have significant implications for disease control strategies. Previous studies demonstrated the persistence of SVA RNA in the tonsil of experimentally or naturally infected animals long after resolution of the clinical disease. Here, we showed that SVA establishes persistent infection in SVA-infected animals, with the tonsil serving as one of the sites of virus persistence. Importantly, persistently infected carrier animals shedding SVA in oral and nasal secretions or feces can serve as sources of infection to other susceptible animals, as evidenced by successful transmission of SVA from persistently infected sows to contact piglets. These findings unveil an important aspect of SVA infection biology, suggesting that persistently infected pigs may function as reservoirs for SVA.
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Portador Sano/veterinaria , Transmisión Vertical de Enfermedad Infecciosa/veterinaria , Infecciones por Picornaviridae/veterinaria , Picornaviridae/patogenicidad , Enfermedades de los Porcinos/transmisión , Animales , Portador Sano/patología , Portador Sano/transmisión , Portador Sano/virología , Enfermedad Crónica , Femenino , Tonsila Palatina/virología , Infecciones por Picornaviridae/patología , Infecciones por Picornaviridae/transmisión , Infecciones por Picornaviridae/virología , Recurrencia , Estrés Fisiológico , Porcinos , Enfermedades de los Porcinos/patología , Enfermedades de los Porcinos/virología , Viremia/patología , Viremia/transmisión , Viremia/veterinaria , Viremia/virología , Esparcimiento de VirusRESUMEN
Seneca Valley virus (SVV) has been identified as the causative agent of SVV-associated vesicular disease (SAVD). To investigate the pathogenicity of two newly isolated SVV strains (GD-S5/2018 and GD04/2017) in China, experimental infections of pigs were performed. In pig experiments, both SVV strains successfully infected all animals, evidenced by presence of virus shedding and robust protective antibody responses. SVV GD-S5/2018 infection resulted in characteristic clinical signs, and ulcerative lesions on the tongue and gums. However, SVV GD04/2017 did not cause any clinical symptoms except depression in pigs during the experiment. Taken together, these results demonstrate that SVV GD-S5/2018 is a virulent strain for pigs, whereas SVV GD04/2017 is nearly avirulent. The established animal models for SVV infection will be utilized to dissect the immunity and pathogenesis, and develop vaccines and antivirals.
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Infecciones por Picornaviridae/veterinaria , Picornaviridae/patogenicidad , Enfermedad Vesicular Porcina/patología , Enfermedad Vesicular Porcina/virología , Animales , China , Picornaviridae/aislamiento & purificación , Infecciones por Picornaviridae/patología , Infecciones por Picornaviridae/virología , Porcinos , VirulenciaRESUMEN
Enteric viruses infect the mammalian gastrointestinal tract which is home to a diverse community of intestinal bacteria. Accumulating evidence suggests that certain enteric viruses utilize these bacteria to promote infection. While this is not surprising considering their proximity, multiple viruses from different viral families have been shown to bind directly to bacteria or bacterial components to aid in viral replication, pathogenesis, and transmission. These data suggest that the concept of a single virus infecting a single cell, independent of the environment, needs to be reevaluated. In this review, I will discuss the current knowledge of enteric virus-bacterial interactions and discuss the implications for viral pathogenesis and transmission.
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Tracto Gastrointestinal/virología , Interacciones Microbianas , Microbiota , Virus , Animales , Tracto Gastrointestinal/microbiología , Interacciones Microbiota-Huesped/inmunología , Humanos , Evasión Inmune , Picornaviridae/crecimiento & desarrollo , Picornaviridae/patogenicidad , Infecciones por Picornaviridae/inmunología , Infecciones por Picornaviridae/microbiología , Infecciones por Picornaviridae/transmisión , Reoviridae/crecimiento & desarrollo , Reoviridae/patogenicidad , Infecciones por Reoviridae/inmunología , Infecciones por Reoviridae/microbiología , Infecciones por Reoviridae/transmisión , Retroviridae/crecimiento & desarrollo , Retroviridae/patogenicidad , Infecciones por Retroviridae/inmunología , Infecciones por Retroviridae/microbiología , Infecciones por Retroviridae/transmisión , Virosis/inmunología , Virosis/microbiología , Virosis/transmisión , Replicación Viral , Virus/crecimiento & desarrollo , Virus/patogenicidadRESUMEN
Saffold virus (SAFV) is classified into the Cardiovirus genus of the Picornaviridae family. Up to now, eleven genotypes have been identified however, their clinical significance remains unclear. Here, we investigated the presence of SAFV in asymptomatic patients admitted for adenoidectomy. A total of 70 adenoid tissue samples were collected from children with clinical symptoms caused by hypertrophy of adenoids but without symptoms of airway infection. Samples were investigated for SAFV by RT-nested PCR and sequence analysis. Eleven of 70 (15.7%) samples were positive for SAFV. Nasopharyngeal swabs were available from 45 children just before surgery. SAFV was rarely found and only in children with SAFV-positive adenoids 2/8. Our findings indicate that the presence of SAFV seems to be more frequent in adenoid tissue than expected. This could support the notion of a longer than previously anticipated persistence of SAFV nucleic acids in the respiratory tract and possibly a chronic infection. Further investigations are necessary to establish the role of SAFV infection in humans.