Detection and Genetic Characterization of Deltacoronavirus in Pigs, Ohio, USA, 2014
01 Jul 2014-Emerging Infectious Diseases (Centers for Disease Control and Prevention)-Vol. 20, Iss: 7, pp 1227-1230
TL;DR: The complete genome sequence and phylogenetic analysis of the virus confirmed that the virus is closely related to a porcine deltacoronavirus (porcine coronavirus HKU15) reported in Hong Kong in 2012.
Abstract: In Ohio, United States, in early 2014, a deltacoronavirus was detected in feces and intestine samples from pigs with diarrheal disease. The complete genome sequence and phylogenetic analysis of the virus confirmed that the virus is closely related to a porcine deltacoronavirus (porcine coronavirus HKU15) reported in Hong Kong in 2012.
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TL;DR: A comprehensive understanding of the pathogenic characteristics of epidemic or endemic PEDV strains is needed to prevent and control the disease in affected regions and to develop an effective vaccine.
Abstract: Porcine epidemic diarrhea virus (PEDV), a member of the genera Alphacoronavirus in the family Coronaviridae, causes acute diarrhea/vomiting, dehydration and high mortality in seronegative neonatal piglets. For the last three decades, PEDV infection has resulted in significant economic losses in the European and Asian pig industries, but in 2013-2014 the disease was also reported in the US, Canada and Mexico. The PED epidemic in the US, from April 2013 to the present, has led to the loss of more than 10% of the US pig population. The disappearance and re-emergence of epidemic PED indicates that the virus is able to escape from current vaccination protocols, biosecurity and control systems. Endemic PED is a significant problem, which is exacerbated by the emergence (or potential importation) of multiple PEDV variants. Epidemic PEDV strains spread rapidly and cause a high number of pig deaths. These strains are highly enteropathogenic and acutely infect villous epithelial cells of the entire small and large intestines although the jejunum and ileum are the primary sites. PEDV infections cause acute, severe atrophic enteritis accompanied by viremia that leads to profound diarrhea and vomiting, followed by extensive dehydration, which is the major cause of death in nursing piglets. A comprehensive understanding of the pathogenic characteristics of epidemic or endemic PEDV strains is needed to prevent and control the disease in affected regions and to develop an effective vaccine. This review focuses on the etiology, epidemiology, disease mechanisms and pathogenesis as well as immunoprophylaxis against PEDV infection.
354 citations
TL;DR: An up-to-date review of the literature currently available on animal CoVs, focusing on the molecular mechanisms that are responsible for the emergence of novel CoV strains with different antigenic, biologic and/or pathogenetic features is provided.
285 citations
TL;DR: In this article, a review of the evolution of the SARS-CoV-2 modes of transmission, detection techniques and current control and prevention strategies is presented, and the authors conclude that the emergence of a novel coronavirus poses a serious public health threat and possibly carries the potential of causing a major pandemic outbreak in the naive human population.
Abstract: Three major outbreaks of the coronavirus, a zoonotic virus known to cause respiratory disease, have been reported since 2002, including SARS-CoV, MERS-CoV and the most recent 2019-nCoV, or more recently known as SARS-CoV-2. Bats are known to be the primary animal reservoir for coronaviruses. However, in the past few decades, the virus has been able to mutate and adapt to infect humans, resulting in an animal-to-human species barrier jump. The emergence of a novel coronavirus poses a serious global public health threat and possibly carries the potential of causing a major pandemic outbreak in the naive human population. The recent outbreak of COVID-19, the disease caused by SARS-CoV-2, in Wuhan, Hubei Province, China has infected over 36.5 million individuals and claimed over one million lives worldwide, as of 8 October 2020. The novel virus is rapidly spreading across China and has been transmitted to 213 other countries/territories across the globe. Researchers have reported that the virus is constantly evolving and spreading through asymptomatic carriers, further suggesting a high global health threat. To this end, current up-to-date information on the coronavirus evolution and SARS-CoV-2 modes of transmission, detection techniques and current control and prevention strategies are summarized in this review.
197 citations
TL;DR: PEDV can serve as a model to explore the molecular mechanisms of coronavirus evolution and pathogenesis, and the evolution, antigenic relationships and pathologic features of PEDV strains are reviewed.
187 citations
Yuanmei Ma1, Yu Zhang1, Xueya Liang1, Fangfei Lou1, Michael Oglesbee1, Steven Krakowka1, Jianrong Li1 •
TL;DR: It is found that PdCV caused severe diarrhea, vomiting, and dehydration in gnotobiotic and conventional piglets, signs that were clinically indistinguishable from those caused by PEDV and TGEV.
Abstract: A novel porcine deltacoronavirus (PdCV) was first discovered in Ohio and Indiana in February 2014, rapidly spread to other states in the United States and Canada, and caused significant economic loss in the swine industry. The origin and virulence of this novel porcine coronavirus are not known. Here, we characterized U.S. PdCV isolates and determined their virulence in gnotobiotic and conventional piglets. Genome analyses revealed that U.S. PdCV isolates possess unique genetic characteristics and share a close relationship with Hong Kong and South Korean PdCV strains and coronaviruses (CoVs) of Asian leopard cats and Chinese ferret-badgers. The PdCV-positive intestinal content (Ohio CVM1) and the cell culture-adapted PdCV Michigan (MI) strain were orally inoculated into gnotobiotic and/or conventional piglets. Within 1 to 3 days postinfection, profuse watery diarrhea, vomiting, and dehydration were observed. Clinical signs were associated with epithelial necrosis in the gastric pits and small intestine, the latter resulting in severe villous atrophy. Mild interstitial pneumonia was identified in the lungs of PdCV-infected piglets. High levels of viral RNA (8 to 11 log RNA copies/g) were detected in intestinal tissues/luminal contents and feces of infected piglets, whereas moderate RNA levels (2 to 5 log RNA copies/g) were detected in blood, lung, liver, and kidney, indicating multisystemic dissemination of the virus. Polyclonal immune serum against PdCV but not immune serum against porcine epidemic diarrhea virus (PEDV) reacted with PdCV-infected small-intestinal epithelial cells, indicating that PdCV is antigenically distinct from PEDV. Collectively, we demonstrate for the first time that PdCV caused severe gastrointestinal diseases in swine. IMPORTANCE Porcine coronaviruses (CoVs) are major viral infectious diseases of swine. Examples of porcine CoVs include porcine transmissible gastroenteritis coronavirus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine respiratory coronavirus (PRCV). In February 2014, another porcine CoV, porcine deltacoronavirus (PdCV), emerged in Ohio and Indiana and subsequently spread rapidly across the United States and Canada , causing significant economic losses. Here, we report the detailed genetic characterization, phylogeny, and virulence of emergent PdCV strains in the United States. We found that PdCV caused severe diarrhea, vomiting, and dehydration in gnotobiotic and conventional piglets, signs that were clinically indistinguishable from those caused by PEDV and TGEV. In addition to extensive intestinal lesions, PdCV caused significant lesions in the stomach and mild pulmonary lesions that have not been reported for TGEV and PEDV. The finding that PdCV is a significant enteric disease of swine highlights the need to develop effective measures to control this disease.
176 citations
References
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TL;DR: It appears that bats and birds, the warm blooded flying vertebrates, are ideal hosts for the coronavirus gene source and birds for Gammacoronavirus and Deltacor onavirus, to fuel coronav virus evolution and dissemination.
Abstract: Recently, we reported the discovery of three novel coronaviruses, bulbul coronavirus HKU11, thrush coronavirus HKU12, and munia coronavirus HKU13, which were identified as representatives of a novel genus, Deltacoronavirus, in the subfamily Coronavirinae. In this territory-wide molecular epidemiology study involving 3,137 mammals and 3,298 birds, we discovered seven additional novel deltacoronaviruses in pigs and birds, which we named porcine coronavirus HKU15, white-eye coronavirus HKU16, sparrow coronavirus HKU17, magpie robin coronavirus HKU18, night heron coronavirus HKU19, wigeon coronavirus HKU20, and common moorhen coronavirus HKU21. Complete genome sequencing and comparative genome analysis showed that the avian and mammalian deltacoronaviruses have similar genome characteristics and structures. They all have relatively small genomes (25.421 to 26.674 kb), the smallest among all coronaviruses. They all have a single papain-like protease domain in the nsp3 gene; an accessory gene, NS6 open reading frame (ORF), located between the M and N genes; and a variable number of accessory genes (up to four) downstream of the N gene. Moreover, they all have the same putative transcription regulatory sequence of ACACCA. Molecular clock analysis showed that the most recent common ancestor of all coronaviruses was estimated at approximately 8100 BC, and those of Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus were at approximately 2400 BC, 3300 BC, 2800 BC, and 3000 BC, respectively. From our studies, it appears that bats and birds, the warm blooded flying vertebrates, are ideal hosts for the coronavirus gene source, bats for Alphacoronavirus and Betacoronavirus and birds for Gammacoronavirus and Deltacoronavirus, to fuel coronavirus evolution and dissemination.
1,212 citations
"Detection and Genetic Characterizat..." refers background or methods or result in this paper
...On the basis of 2 complete genome sequences from GenBank, of PorCoV HKU15-44 and HKU15-155, we designed 16 pairs of primers to determine the whole genome of extracted RNA samples (OH1987) from Farm 1 (Table 2)....
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...The OH1987 virus differs from HKU15-155 in the spike gene at nt 19469 and in the noncoding region at nt 25044; a 3-nt insertion is present at each location, making the whole-genome sequence of the OH1987 virus 6 nt longer than that of HKU15-155....
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...Phylogenetic analysis of the complete genome of PorCoV HKU15 OH1987 showed that the OH1987 strain clustered with the other 2 PorCoVs, HKU15-155 and HKU15-44, and was distinct from the bird deltacoronaviruses (Figure 1)....
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...Similar to the BLAST search results of partial N and M fragments, the BLAST search of the whole genome of the PorCoV HKU15 OH1987 showed 99% nt identity to PorCoV HKU15-155....
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...In addition, the phylogenetic trees constructed by using the amino acid sequences of the spike glycoprotein and nucleocapsid protein showed that the OH1987 virus clustered with HKU15-155 and HKU15-44 (Figure 2); this finding is in agreement with that in a previous study (1)....
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TL;DR: Coronaviruses possess the largest genomes among all known RNA viruses, with G + C contents varying from 32% to 43%.
Abstract: The drastic increase in the number of coronaviruses discovered and coronavirus genomes being sequenced have given us an unprecedented opportunity to perform genomics and bioinformatics analysis on this family of viruses. Coronaviruses possess the largest genomes (26.4 to 31.7 kb) among all known RNA viruses, with G + C contents varying from 32% to 43%. Variable numbers of small ORFs are present between the various conserved genes (ORF1ab, spike, envelope, membrane and nucleocapsid) and downstream to nucleocapsid gene in different coronavirus lineages. Phylogenetically, three genera, Alphacoronavirus, Betacoronavirus and Gammacoronavirus, with Betacoronavirus consisting of subgroups A, B, C and D, exist. A fourth genus, Deltacoronavirus, which includes bulbul coronavirus HKU11, thrush coronavirus HKU12 and munia coronavirus HKU13, is emerging. Molecular clock analysis using various gene loci revealed that the time of most recent common ancestor of human/civet SARS related coronavirus to be 1999-2002, with estimated substitution rate of 410 -4 to 210 -2 substitutions per site per year. Recombination in coronaviruses was most notable between different strains of murine hepatitis virus (MHV), between different strains of infectious bronchitis virus, between MHV and bovine coronavirus, between feline coronavirus (FCoV) type I and canine coronavirus generating FCoV type II, and between the three genotypes of human
679 citations
"Detection and Genetic Characterizat..." refers background in this paper
...Coronaviruses traditionally were classified into groups 1, 2, and 3 on the basis of their antigenic relationships (2)....
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TL;DR: The molecular and genetic characteristics of the porcine epidemic diarrhoea virus are described, its molecular epidemiology and diagnosis, what vaccines are available, and how PEDV can be treated are discussed.
Abstract: The porcine epidemic diarrhoea virus (PEDV), a member of the Coronaviridae family, causes acute diarrhoea and dehydration in pigs. Although it was first identified in Europe, it has become increasingly problematic in many Asian countries, including Korea, China, Japan, the Philippines, and Thailand. The economic impacts of the PEDV are substantial, given that it results in significant morbidity and mortality in neonatal piglets and is associated with increased costs related to vaccination and disinfection. Recently, progress has been made in understanding the molecular epidemiology of PEDV, thereby leading to the development of new vaccines. In the current review, we first describe the molecular and genetic characteristics of the PEDV. Then we discuss its molecular epidemiology and diagnosis, what vaccines are available, and how PEDV can be treated.
559 citations
TL;DR: Bats and birds are natural reservoirs for providing viral genes during evolution of new virus species and viruses for interspecies transmission and the increased intrusion of humans into wildlife habitats and overcrowding of different wildlife species in wet markets and farms have facilitated the inter species transmission.
479 citations
"Detection and Genetic Characterizat..." refers background in this paper
...Virus from each coronavirus genus has been found in diverse host species, including mammals and birds (3)....
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...Viruses of the Alphacoronavirus, Betacoronavirus, and Deltacoronavirus genera have been detected in swine (3)....
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TL;DR: The finding that the emergent U.S. PEDV strains share unique genetic features at the 5′-untranslated region with a bat coronavirus provided further support of the evolutionary origin of P EDV from bats and potential cross-species transmission.
Abstract: Coronaviruses are known to infect humans and other animals and cause respiratory and gastrointestinal diseases. Here we report the emergence of porcine epidemic diarrhea virus (PEDV) in the United States and determination of its origin, evolution, and genotypes based on temporal and geographical evidence. Histological lesions in small intestine sections of affected pigs and the complete genomic sequences of three emergent strains of PEDV isolated from outbreaks in Minnesota and Iowa were characterized. Genetic and phylogenetic analyses of the three U.S. strains revealed a close relationship with Chinese PEDV strains and their likely Chinese origin. The U.S. PEDV strains underwent evolutionary divergence, which can be classified into two sublineages. The three emergent U.S. strains are most closely related to a strain isolated in 2012 from Anhui Province in China, which might be the result of multiple recombination events between different genetic lineages or sublineages of PEDV. Molecular clock analysis of the divergent time based on the complete genomic sequences is consistent with the actual time difference, approximately 2 to 3 years, of the PED outbreaks between China (December 2010) and the United States (May 2013). The finding that the emergent U.S. PEDV strains share unique genetic features at the 5′-untranslated region with a bat coronavirus provided further support of the evolutionary origin of PEDV from bats and potential cross-species transmission. The data from this study have important implications for understanding the ongoing PEDV outbreaks in the United States and will guide future efforts to develop effective preventive and control measures against PEDV. IMPORTANCE The sudden emergence of porcine epidemic diarrhea virus (PEDV), a coronavirus, for the first time in the United States causes significant economic and public health concerns. Since its recognition in May 2013, PEDV has rapidly spread across the United States, resulting in high mortality in piglets in more than 17 States now. The ongoing outbreaks of Middle East respiratory syndrome coronavirus in humans from countries in or near the Arabian Peninsula and the historical deadly nature of the 2002 outbreaks of severe acute respiratory syndrome coronavirus create further anxiety over the emergence of PEDV in the United States due to the lack of scientific information about the origin and evolution of this emerging coronavirus. Here we report the detailed genetic characterization, origin, and evolution of emergent PEDV strains in the United States. The results provide much needed information to devise effective preventive and control strategies against PEDV in the United States.
442 citations