Complete Genome Analysis of Porcine Enterovirus B Isolated in Korea

Moon, Heejang; Song, Daesub; Seon, Bo Hyeon; Kim, Hye-Kwon; Park, Seongjun; An, Dong-Jun; Kim, Jong-Man; Kang, Bo-Kyu; Park, Bong‐Kyun

doi:10.1128/jvi.01548-12

Cited by 22 publications

(19 citation statements)

References 4 publications

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“…The EV genus includes viruses that infect humans (species A to D), bovines (species E and F), swine (species G), and nonhuman primates (species A, B, D, H, and J). Currently, EV species G (EVG) is divided into 11 types, EV-G1 to EV-G11 (2)(3)(4). Enteroviruses are small nonenveloped viruses that contain positive-strand RNA genomes of approximately 7,400 to 7,500 nucleotides (nt).…”

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A Naturally Occurring Recombinant Enterovirus Expresses a Torovirus Deubiquitinase

Shang

Misra

Hause

et al. 2017

J Virol

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Enteroviruses (EVs) are implicated in a wide range of diseases in humans and animals. In this study, a novel enterovirus (enterovirus species G [EVG]) (EVG 08/NC_USA/2015) was isolated from a diagnostic sample from a neonatal pig diarrhea case and identified by using metagenomics and complete genome sequencing. The viral genome shares 75.4% nucleotide identity with a prototypic EVG strain (PEV9 UKG/410/73). Remarkably, a 582-nucleotide insertion, flanked by 3C pro cleavage sites at the 5= and 3= ends, was found in the 2C/3A junction region of the viral genome. This insertion encodes a predicted protease with 54 to 68% amino acid identity to torovirus (ToV) papain-like protease (PLP) (ToV-PLP). Structural homology modeling predicts that this protease adopts a fold and a catalytic site characteristic of minimal PLP catalytic domains. This structure is similar to those of core catalytic domains of the foot-and-mouth disease virus leader protease and coronavirus PLPs, which act as deubiquitinating and deISGylating (interferon [IFN]-stimulated gene 15 [ISG15]-removing) enzymes on host cell substrates. Importantly, the recombinant ToV-PLP protein derived from this novel enterovirus also showed strong deubiquitination and deISGylation activities and demonstrated the ability to suppress IFN-␤ expression. Using reverse genetics, we generated a ToV-PLP knockout recombinant virus. Compared to the wild-type virus, the ToV-PLP knockout mutant virus showed impaired growth and induced higher expression levels of innate immune genes in infected cells. These results suggest that ToV-PLP functions as an innate immune antagonist; enterovirus G may therefore gain fitness through the acquisition of ToV-PLP from a recombination event.IMPORTANCE Enteroviruses comprise a highly diversified group of viruses. Genetic recombination has been considered a driving force for viral evolution; however, recombination between viruses from two different orders is a rare event. In this study, we identified a special case of cross-order recombination between enterovirus G (order Picornavirales) and torovirus (order Nidovirales). This naturally occurring recombination event may have broad implications for other picornaviral and/or nidoviral species. Importantly, we demonstrated that the exogenous ToV-PLP gene that was inserted into the EVG genome encodes a deubiquitinase/ deISGylase and potentially suppresses host cellular innate immune responses. Our results provide insights into how a gain of function through genetic recombination, in particular cross-order recombination, may improve the ability of a virus to evade host immunity.KEYWORDS enterovirus G, torovirus, genetic recombination, papain-like protease, deubiquitinase

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confidence: 99%

A Naturally Occurring Recombinant Enterovirus Expresses a Torovirus Deubiquitinase

Shang

Misra

Hause

et al. 2017

J Virol

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“…The 14 currently available EV-G complete genomes from GenBank (with VP1-based genotypes: 1-6, 8-10) were identified from swine in the UK, Belgium, China, Hungary, Vietnam, South Korea and the USA [9,13,[27][28][29][30][31][32][33]. Currently, EV-G genotypes are classified solely by the VP1.…”

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A porcine enterovirus G associated with enteric disease contains a novel papain-like cysteine protease

Knutson

Velayudhan²,

Marthaler

2017

Journal of General Virology

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Identification of unknown pathogens in pigs displaying enteric illness is difficult due to the large diversity of bacterial and viral species found within faecal samples. Current methods often require bacterial or viral isolation, or testing only a limited number of known species using quantitative PCR analysis. Herein, faeces from two 25-day-old piglets with diarrhoea from Texas, USA, were analysed by metagenomic next-generation sequencing to rapidly identify possible pathogens. Our analysis included a bioinformatics pipeline of rapid short-read classification and de novo genome assembly which resulted in the identification of a porcine enterovirus G (EV-G), a complete genome with substantial nucleotide differences (>30 %) among current sequences, and a novel non-structural protein similar in sequence to the Torovirus papain-like cysteine protease (PLpro). This discovery led to the identification and circulation of an EV-G with a novel PLpro in the USA that has not been previously reported.

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“…Although PEVs are detected in porcine fecal samples, its precise role as an enteric pathogen remains largely unknown [8]. Moreover, PEVs are detected in both diarrheic and clinically healthy pigs [24][25][26]. Therefore, further studies should address the enteropathogenicity of PEVs.…”

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Molecular epidemiology of Korean porcine sapeloviruses

et al. 2013

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To evaluate the prevalence and genetic diversity of porcine sapeloviruses (PSVs) in Korea, a total of 100 diarrhea fecal samples from pigs were analyzed by RT-PCR and nested PCR assays with primer pairs specific for the VP1 gene. Overall, 34 % of the diarrhea samples tested positive for PSV, and a high proportion of infections occurred along with a variety of other enteric viruses and bacteria. Genomic and phylogenetic analysis of the VP1 genes revealed pronounced genetic diversities between PSVs from Korean and elsewhere. Our results indicate that PSV infections are very common in Korean pigs with diarrhea. The infecting strains are genetically diverse.

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Complete Genome Analysis of Porcine Enterovirus B Isolated in Korea

Cited by 22 publications

References 4 publications

A Naturally Occurring Recombinant Enterovirus Expresses a Torovirus Deubiquitinase

A Naturally Occurring Recombinant Enterovirus Expresses a Torovirus Deubiquitinase

A porcine enterovirus G associated with enteric disease contains a novel papain-like cysteine protease

Molecular epidemiology of Korean porcine sapeloviruses

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