Complete genome sequence analysis of Seneca Valley virus-001, a novel oncolytic picornavirus

Hales, Laura M.; Knowles, Nick J.; Reddy, P. Seshidar; Xu, Li; Hay, Carl; Hallenbeck, Paul L.

doi:10.1099/vir.0.83570-0

Cited by 300 publications

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“…The SVA genome is ϳ7.2 kb in length and contains a unique open reading frame encoding a large polyprotein (2,181 amino acids [aa]), which is cleaved to produce 12 mature proteins (5=-L-1A-1B-1C-1D-2A-2B-2C-3A-3B-3C-3D-3=) (1). Among the picornaviruses, SVA is closely related to members of the genus Cardiovirus (1), including the encephalomyocarditis virus (ECMV) and the theiloviruses, which are known to infect a wide range of vertebrate animals, including pigs, mice, and humans (2).…”

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Detection of the Emerging Picornavirus Senecavirus A in Pigs, Mice, and Houseflies

et al. 2016

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c Senecavirus A (SVA) is an emerging picornavirus that has been recently associated with an increased number of outbreaks of vesicular disease and neonatal mortality in swine. Many aspects of SVA infection biology and epidemiology remain unknown. Here, we present a diagnostic investigation conducted in swine herds affected by vesicular disease and increased neonatal mortality. Clinical and environmental samples were collected from affected and unaffected herds and were screened for the presence of SVA by real-time reverse transcriptase PCR and virus isolation. Notably, SVA was detected and isolated from vesicular lesions and tissues of affected pigs, environmental samples, mouse feces, and mouse small intestine. SVA nucleic acid was also detected in houseflies collected from affected farms and from a farm with no history of vesicular disease. Detection of SVA in mice and housefly samples and recovery of viable virus from mouse feces and small intestine suggest that these pests may play a role on the epidemiology of SVA. These results provide important information that may allow the development of improved prevention and control strategies for SVA.

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“…enecavirus A (SVA) is a single-stranded positive-sense RNA virus of the genus Senecavirus within the family Picornaviridae (1). The SVA genome is ϳ7.2 kb in length and contains a unique open reading frame encoding a large polyprotein (2,181 amino acids [aa]), which is cleaved to produce 12 mature proteins (5=-L-1A-1B-1C-1D-2A-2B-2C-3A-3B-3C-3D-3=) (1).…”

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Detection of the Emerging Picornavirus Senecavirus A in Pigs, Mice, and Houseflies

et al. 2016

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“…The virus was first described as a contaminant of a PER C6 cell line (2). The virus encodes one polyprotein that is posttranslationally processed by virus-encoded proteases into 4 structural (VP1 to VP4) and 7 nonstructural (2A to 2C and 3A to 3D) proteins (2,3). The pathogenic role of these SVA proteins is unknown, but VP1 is considered to be the most immunogenic protein in viruses of the Picornaviridae family (4,5).…”

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Serological and Molecular Detection of Senecavirus A Associated with an Outbreak of Swine Idiopathic Vesicular Disease and Neonatal Mortality

et al. 2016

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bWe performed a longitudinal field study in a swine breeding herd that presented with an outbreak of vesicular disease (VD) that was associated with an increase in neonatal mortality. Initially, a USDA Foreign Animal Disease (FAD) investigation confirmed the presence of Senecavirus A (SVA) and ruled out the presence of exotic agents that produce vesicular lesions, e.g., foot-andmouth disease virus and others. Subsequently, serum samples, tonsil swabs, and feces were collected from sows (n ‫؍‬ 22) and their piglets (n ‫؍‬ 33) beginning 1 week after the onset of the clinical outbreak and weekly for 6 weeks. The presence of SVA RNA was evaluated in all specimens collected by reverse transcriptase quantitative PCR (RT-qPCR) targeting a conserved region of the 5= untranslated region (5=-UTR). The serological response (IgG) to SVA was evaluated by the weekly testing of sow and piglet serum samples on a SVA VP1 recombinant protein (rVP1) indirect enzyme-linked immunosorbent assay (ELISA). The rVP1 ELISA detected seroconversion against SVA in clinically affected and non-clinically affected sows at early stages of the outbreak as well as maternal SVA antibodies in offspring. Overall, the absence of vesicles (gross lesions) in SVA-infected animals and the variability of RT-qPCR results among specimen type demonstrated that a diagnostic algorithm based on the combination of clinical observations, RT-qPCR in multiple diagnostic specimens, and serology are essential to ensure an accurate diagnosis of SVA. S enecavirus A (SVA), formerly Seneca Valley virus (SVV), is a nonenveloped, single-stranded, positive-sense RNA virus that belongs to the genus Senecavirus in the family Picornaviridae (1). The virus was first described as a contaminant of a PER C6 cell line (2). The virus encodes one polyprotein that is posttranslationally processed by virus-encoded proteases into 4 structural (VP1 to VP4) and 7 nonstructural (2A to 2C and 3A to 3D) proteins (2, 3). The pathogenic role of these SVA proteins is unknown, but VP1 is considered to be the most immunogenic protein in viruses of the Picornaviridae family (4, 5).Idiopathic vesicular disease (IVD), a sporadic and transient condition affecting swine, has been reported in pigs in Australia, New Zealand, and the United States (6-8). It was not until 2007 that the presence of SVA was linked with IVD outbreaks in Canada (9). Most recently, SVA was detected in sporadic and transient outbreaks of IVD in the United States, Brazil, and China (10-13). Lesions observed in cases of IVD associated with SVA infection are characterized by vesicle formations and epidermal erosions that progress to ulcers of the coronary band, oral cavity, and nasal planum. Affected animals present transient fever and lameness. Vesicular lesions in pigs resemble those in other foreign vesicular diseases, such as foot-and-mouth disease (FMD), vesicular stomatitis (VS), swine vesicular disease (SVD), and vesicular exanthema of swine (VES). In addition, numerous reports associate the presence of SVA with increased ne...

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“…It was found as a contaminant in PER.C6 cell cultures, and its natural host has not yet been definitively identified, but a number of closely related viruses have been isolated from pigs (16). The complete genome sequence of SVV-001 (16) and the crystal structure of the virus capsid (52) have now been determined. The virus is most closely related to the cardioviruses, but there are some significant differences (see below), and hence it has been recommended that the virus is classified as a new species within a new genus (Senecavirus) of the Picornaviridae.…”

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Structural Features of the Seneca Valley Virus Internal Ribosome Entry Site (IRES) Element: a Picornavirus with a Pestivirus-Like IRES

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Gomwalk

et al. 2011

J Virol

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The RNA genome of Seneca Valley virus (SVV), a recently identified picornavirus, contains an internal ribosome entry site (IRES) element which has structural and functional similarity to that from classical swine fever virus (CSFV) and hepatitis C virus, members of the Flaviviridae. The SVV IRES has an absolute requirement for the presence of a short region of virus-coding sequence to allow it to function either in cells or in rabbit reticulocyte lysate. The IRES activity does not require the translation initiation factor eIF4A or intact eIF4G. The predicted secondary structure indicates that the SVV IRES is more closely related to the CSFV IRES, including the presence of a bipartite IIId domain. Mutagenesis of the SVV IRES, coupled to functional assays, support the core elements of the IRES structure model, but surprisingly, deletion of the conserved IIId 2 domain had no effect on IRES activity, including 40S and eIF3 binding. This is the first example of a picornavirus IRES that is most closely related to the CSFV IRES and suggests the possibility of multiple, independent recombination events between the genomes of the Picornaviridae and Flaviviridae to give rise to similar IRES elements.Seneca Valley virus (SVV) is a recently discovered member of the picornavirus family. It was found as a contaminant in PER.C6 cell cultures, and its natural host has not yet been definitively identified, but a number of closely related viruses have been isolated from pigs (16). The complete genome sequence of SVV-001 (16) and the crystal structure of the virus capsid (52) have now been determined. The virus is most closely related to the cardioviruses, but there are some significant differences (see below), and hence it has been recommended that the virus is classified as a new species within a new genus (Senecavirus) of the Picornaviridae.SVV-001 and two of the related viruses (isolates 1278 and 66289) were inoculated into pigs; evidence of viral replication was obtained for all three viruses and for transmission of isolate 66289. However, in none of the experiments was any sign of illness observed (unpublished data and personal communication from J. Landgraf, USDA). An important feature of SVV is its ability to replicate selectively within human tumor cells. Owing to this novel activity and lack of observed pathogenicity in animals and humans, there is interest in using SVV as an oncolytic virus against neuroendocrine cancers (39), for which it is currently in clinical trials.All picornaviruses have a positive-sense, single-stranded RNA genome that is infectious and has to act both as an mRNA and as a template for RNA replication (32). Picornavirus RNA includes a single large open reading frame (ORF), encoding a polyprotein, which is flanked by a long 5Ј untranslated region (UTR) of approximately 600 to 1,300 nucleotides (nt) (depending on the virus) plus a shorter 3Ј UTR (Ͻ100 nt) with a poly(A) tail. The viral RNA lacks the 5Ј m 7 GpppN... cap structure found on all eukaryotic cytoplasmic mRNAs. Instead, a small virus-enco...

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Complete genome sequence analysis of Seneca Valley virus-001, a novel oncolytic picornavirus

Cited by 300 publications

References 50 publications

Detection of the Emerging Picornavirus Senecavirus A in Pigs, Mice, and Houseflies

Detection of the Emerging Picornavirus Senecavirus A in Pigs, Mice, and Houseflies

Serological and Molecular Detection of Senecavirus A Associated with an Outbreak of Swine Idiopathic Vesicular Disease and Neonatal Mortality

Structural Features of the Seneca Valley Virus Internal Ribosome Entry Site (IRES) Element: a Picornavirus with a Pestivirus-Like IRES

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