Identification and characterization of atypical porcine pestivirus genomes in newborn piglets with congenital tremor in China.
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ABSTRACT:
SUBMITTER: Shen H
PROVIDER: S-EPMC5974529 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Pestiviruses are highly variable RNA viruses belonging to the continuously growing family Flaviviridae. A genetically very distinct pestivirus was recently discovered in the USA, designated atypical porcine pestivirus (APPV). Here, a screening of 369 sera from apparently healthy adult pigs demonstrated the existence of APPV in Germany with an estimated individual prevalence of 2.4% and ~10% at farm level. Additionally, APPV genomes were detected in newborn piglets affected by congenital tremor (CT), but genomes were absent in unaffected piglets. High loads of genomes were identified in glandular epithelial cells, follicular centers of lymphoid organs, the inner granular cell layer of the cerebellum, as well as in the trigeminal and spinal ganglia. Retrospective analysis of cerebellum samples from 2007 demonstrated that APPV can be found in piglets with CT of unsolved aetiology. Determination of the first European APPV complete polyprotein coding sequence revealed 88.2% nucleotide identity to the APPV sequence from the USA. APPV sequences derived from different regions in Germany demonstrated to be highly variable. Taken together, the results of this study strongly suggest that the presence of APPV genomes in newborn piglets correlates with CT, while no association with clinical disease could be observed in viremic adult pigs.
| S-EPMC4904412 | biostudies-literature
Project description:Congenital tremor type A-II in piglets has been regarded as a transmissible disease since the 1970s, possibly caused by a very recently-described virus: atypical porcine pestivirus (APPV). Here, we describe several strains of APPV in piglets with clinical signs of congenital tremor (10 of 10 farms tested). Piglets on a farm with no history of congenital tremor were PCR-negative for the virus. To demonstrate a causal relationship between APPV and disease, three gilts were inoculated via intramuscular injection at day 32 of pregnancy. In two of the three litters, vertical transmission of the virus occurred. Clinical signs of congenital tremor were observed in APPV-infected newborns, yet also two asymptomatic carriers were among the offspring. Piglets of one litter were PCR-negative for the virus, and these piglets were all without congenital tremors. Long-term follow up of farm piglets born with congenital tremors showed that the initially high viremia in serum declines at five months of age, but shedding of the virus in feces continues, which explains why the virus remains present at affected farms and causes new outbreaks. We conclude that trans-placental transmission of APPV and subsequent infection of the fetuses is a very likely cause of congenital tremor type A-II in piglets.
| S-EPMC5086607 | biostudies-literature
Project description:Recently, piglets from a high-health status farm began exhibiting congenital tremors, high preweaning mortality and incidence of splayed legs. Postmortem histological examination identified a small number of scattered white matter vacuoles in the cerebellum and underlying brainstem of affected piglets. Presence of potential viral sources associated with this neurologic condition was initially infirmed using quantitative PCR for atypical porcine pestivirus (APPV), porcine teschovirus, and porcine sapelovirus. Using metagenomic analysis, APPV was identified as the main microbial species in serum obtained from piglets affected by congenital tremor. These piglets had higher preweaning mortality rates (46.4% vs. 15.3%) and incidence of splayed legs (33.0% vs. 0.8 %) compared to unaffected piglets. Piglets affected by congenital tremor had higher viral titer (P < 0.15) and larger birth weights (P < 0.05) compared to normal litter mates. Whole-genome sequencing and genome assembly of the novel APPV strain (MK728876) was carried out using Oxford Nanopore and related bioinformatics pipelines. Phylogenic analysis demonstrated that this strain along with other completely sequenced APPV strains were grouped into 2 clades, both including strains-inducing congenital tremor. Strains appear to cluster based on region but there were still significant differences within regions. Future research needs to address potential underdiagnosis due to genetic diversity but also to understand mode of transmission, variation in virulence, and the role of host genetics in APPV susceptibility.
| S-EPMC6776285 | biostudies-literature
Project description:BackgroundCongenital tremor (CT) type A-II is a neurological disorder characterized by tremor of the head and body of newborn piglets. The suggested causative agent of the disease is the recently found atypical porcine pestivirus (APPV). The virus has been detected in piglets suffering from congenital tremor in central Europe, South and North America and in China but no studies has so far been performed in the Nordic countries. The overarching goal of this study was to investigate if APPV is present in the brain tissue of Swedish piglets suffering from congenital tremor. From June 2017 - June 2018, 15 piglets from four Swedish farms with ongoing outbreaks of congenital tremor and 13 piglets with splay leg originating from four different farms, were investigated for presence of APPV RNA in brain tissue. Matched healthy control piglets (n = 8) were also investigated. Two APPV-specific RT-qPCR methods targeting the NS3 and NS5B region, respectively, were used. A retrospective study was performed on material from Swedish piglets with congenital tremor sampled in 2004 (n = 11) and 2011/2012 (n = 3) using the described APPV-specific RT-qPCR methods. The total number of piglets with signs of CT in this study was 29.ResultsAtypical porcine pestivirus-RNA was detected in 93% (27/29) of the piglets suffering from congenital tremor. All piglets with congenital tremor from 2004 (n = 11) and 2012 (n = 3) were PCR-positive with respect to APPV, whereas, all of the healthy controls (n = 11) were negative. The piglets with congenital tremor sampled 2017-2018 had an odds ratio of 91.8 (95% CI 3.9128 to 2153.7842, z = 2.807, P = 0.0050) to test positive for APPV by qRT-PCR compared to the healthy piglets (Fishers exact test p < 0.0001). These findings make it interesting to continue investigating APPV in the Swedish pig-population.ConclusionThis is the first description of atypical porcine pestivirus in piglets suffering from congenital tremor type A-II in Sweden and the Nordic countries. The virus has been present in the Swedish pig population since at least 2004.
| S-EPMC7389371 | biostudies-literature
Project description:Atypical porcine pestivirus (APPV) was identified and associated with congenital tremor (CT) type A-II in new born piglets and has been reported in many countries. In China, the first APPV identification in swine herds was reported in Guangdong province in 2016. To investigate the genetic characteristics of APPV in Guangxi province, 53 tissue samples from neonatal piglets with CT were collected and detected from October 2017 to May 2019. Five APPV strains which were named as GX04/2017, GX01-2018, GX02-2018, GX01-2019 and GX02-2019 were obtained. Sequence analysis revealed that all six APPV strains from Guangxi province, including five strains from this study and one from a previous report, shared 83.3%-97.5% nucleotide identity of complete genome and 91.7%-99.1% amino acid identity of the open reading frame (ORF), and shared 77.7%-97.7% nucleotide identity of complete genome and 90.6%-99.3% amino acid identity of ORF with reference strains. Phylogenetic analysis indicated that all APPV strains could be divided into three clades based on the complete genome, Npro , Erns and E2 gene sequences, respectively; and the APPV strains from Guangxi province distributed in two clades (clades I and II). No sign of recombination was observed from Guangxi strains. Evolution analysis performed on the complete genome of 58 APPV strains showed that America, Europe and Asia strains during 2006-2019 evolved at a mean rate of 1.37 × 10-4 substitutions/site/year, and the most recent common ancestor (tMRCA) of them was estimated as 1,700.5 years ago. The findings of this study indicated that there existed a high degree of genetic diversity of APPV from Guangxi province, Southern China, which provided important information on the epidemiological features and evolutionary relationships of APPV.
| S-EPMC8136935 | biostudies-literature
Project description:Atypical porcine pestivirus (APPV) is an RNA virus newly discovered from swine in Asia, Europe, and the Americas. This novel virus has been confirmed as the cause of congenital tremor (CT) in piglets, which causes extensive economic losses to the swine industry. To investigate the genetic diversity and evolutionary relationship of APPV in China, 83 piglet samples with severe CT clinical signs were obtained from 12 commercial swine farms in 3 provinces of Southern China. RT-PCR revealed that the positive rates of APPV were as high as 100% (12/12) for the swine farms and 90.4% (75/83) for the samples. Subsequently, 21 positive samples and 3 positive samples were selected for partial E2 gene and complete polyprotein gene sequencing, respectively. Phylogenetic analysis showed that 62.5% of the sequences belonged to a novel APPV clade provisionally named genotype 3, which showed 81.0-82.1% sequence identity to genotypes 1 and 2. Amino acid sequence alignment showed that E2 protein of genotype 3 has three specific mutation sites, namely I19V, Y82F, and N107G. The results of the present study demonstrate that a novel APPV subgenotype, which is widely distributed in severe CT clinical samples in Southern China, was genetically diverse. We advocate for the inclusion of genotype 3 during revision of the APPV typing method.
| S-EPMC6596314 | biostudies-literature
Project description:Atypical porcine pestivirus (APPV) was first discovered in North America in 2015 and was later shown to be associated with congenital tremor (CT) in piglets. CT is an occasional challenge in some Danish sow herds. Therefore, we initiated an observational case control study to clarify a possible relationship between CT and APPV in Danish pig production. Blood samples were collected from piglets affected by CT (n = 55) in ten different sow herds and from healthy piglets in five sow herds without a history of CT piglets (n = 25), as well as one sow herd with a sporadic occurrence of CT (n = 5). APPV was detected by RT-qPCR in all samples from piglets affected by CT and in three out of five samples from piglets in the herd with a sporadic occurrence of CT. In the herds without a history of CT, only one out of 25 piglets were positive for APPV. In addition, farmers or veterinarians in CT-affected herds were asked about their experience of the issue. CT is most often seen in gilt litters, and a substantial increase in pre-weaning mortality is only observed in severe cases. According to our investigations, APPV is a common finding in piglets suffering from CT in Denmark.
| S-EPMC8142981 | biostudies-literature
Project description:Atypical porcine pestivirus Genome sequencing
| PRJNA577836 | ENA
Project description:Pestiviruses are highly variable RNA viruses. A growing number of novel pestiviruses has been discovered in domestic and wild species in the last two decades. Recently, a novel atypical porcine pestivirus (APPV) linked with the development of congenital tremor (CT) in neonatal pigs was described in Europe and the Americas. Here, the first Asian APPV complete polyprotein coding sequence was assembled from serum samples from newborn piglets affected with CT in Southern China, and termed APPV_GD. 14 organ samples from affected piglets were analyzed by quantitative RT-PCR (qRT-PCR) to investigate the tissue tropism of APPV, and 135 serum samples from pigs from 10 farms were used for identifying APPV in adult pigs. The highest genome loads were found in submaxillary lymph nodes, and PCR-based detection showed that APPV genomes were present in seven samples from five farms. A phylogenetic tree was constructed based on the full-length genomes of the pestiviruses, and APPV_GD appeared on a new branch with another newly discovered APPV. Nucleotide identity analysis demonstrated that APPV_GD shared the highest nucleotide sequence identity with a German APPV. Bayesian inference was performed using 25 partial sequences of the APPV NS5B gene (528 bp) isolated from four countries in recent years. According to this analysis, the most recent common ancestor (tMRCA) of the current APPV strains might have emerged in Germany and then diversified and spread to Asia, the Americas, and other countries in Europe. However, the result of bayesian inference could change when more APPV strains are isolated in the future. The present study is the first to report APPV in China and infers the origin and dissemination of the current strains of the virus.
| S-EPMC5425480 | biostudies-literature
Project description:The presence of congenital tremor (CT) type A-II in newborn piglets, caused by atypical porcine pestivirus (APPV), has been a focus since 2016. However, the source, evolutionary history, and transmission pattern of APPV in China remain poorly understood. In this study, we undertook phylogenetic analyses based on available complete E2 gene sequences along with 98 newly sequenced E2 genes between 2016 and 2020 in China within the context of global genetic diversity. The phylogenies revealed four distinct lineages of APPV, and interestingly, all lineages could be detected in China with the greatest diversity. Bayesian phylogenetic analyses showed that the E2 gene evolves at a mean rate of 1.22 × 10-3 (8.54 × 10-4-1.60 × 10-3) substitutions/site/year. The most recent common ancestor for APPVs is dated to 1886 (1837-1924) CE, somewhat earlier than the documented emergence of CT (1922 CE). Our phylogeographic analyses suggested that the APPV population possibly originated in the Netherlands, a country with developed livestock husbandry, and was introduced into China during the period 1837-2010. Guangdong, as a primary seeding population together with Central and Southwest China as epidemic linkers, was responsible for the dispersal of APPVs in China. The transmission pattern of "China lineages" (lineage 3 and lineage 4) presented a "south to north" movement tendency, which was likely associated with the implementation of strict environmental policy in China since 2000. Reconstruction of demographic history showed that APPV population size experienced multiple changes, which correlated well with the dynamic of the number of pigs in the past decades in China. Besides, positively selected pressure and geography-driven adaptation were supposed to be key factors for the diversification of APPV lineages. Our findings provide comprehensive insights into the diversity and spatiotemporal dynamic of APPV in China.
| S-EPMC9263985 | biostudies-literature