Proteome analysis of porcine epidemic diarrhea virus (PEDV)‐infected Vero cells

Porcine epidemic diarrhea virus (PEDV) causes an acute, highly contagious, and devastating viral enteric disease with a high mortality rate in suckling pigs. A large‐scale outbreak of PED occurred in China in 2010, with PEDV emerging in the United States in 2013 and spreading rapidly, posing significant economic and public health concerns. In this study, LC–MS/MS coupled to iTRAQ labeling was used to quantitatively identify differentially expressed cellular proteins in PEDV‐infected Vero cells. We identified 49 differentially expressed cellular proteins, of which 8 were upregulated and 41 downregulated. These differentially expressed proteins were involved in apoptosis, signal transduction, and stress responses. Based on these differentially expressed proteins, we propose that PEDV might utilize apoptosis and extracellular signal regulated kinases pathways for maximum viral replication. Our study is the first attempt to analyze the protein profile of PEDV‐infected cells by quantitative proteomics, and we believe our findings provide valuable information with respect to better understanding the host response to PEDV infection.     

Comparison of lentiviruses pseudotyped with S proteins from coronaviruses and cell tropisms of porcine coronaviruses

The surface glycoproteins of coronaviruses play an important role in receptor binding and cell entry. Different coronaviruses interact with their specific receptors to enter host cells. Lentiviruses pseudotyped with their spike proteins (S) were compared to analyze the entry efficiency of various coronaviruses. Our results indicated that S proteins from different coronaviruses displayed varied abilities to mediate pseudotyped virus infection. Furthermore, the cell tropisms of porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) have been characterized by live and pseudotyped viruses. Both live and pseudoviruses could infected Vero- CCL-81 (monkey kidney), Huh-7 (human liver), and PK-15 (pig kidney) cells efficiently. CCL94 (cat kidney) cells could be infected efficiently by TGEV but not PEDV. Overall, our study provides new insights into the mechanisms of viral entry and forms a basis for antiviral drug screening.

Open image in new window

     

Complete genome sequence of a novel porcine epidemic diarrhea virus in South china

Since early 2010, outbreaks of porcine epidemic diarrhea (PED) have been observed frequently in immunized swine herds in southern China. The suckling piglets are particularly susceptible to porcine epidemic diarrhea virus (PEDV), with a high mortality rate (90%). Recently, a virulent PEDV strain, GD-A, was isolated from an immunized-swine breeding farm in Guangdong, China. This report describes the complete genome sequence of GD-A, and the data will provide important insights into the variation of PEDV field isolates in southern China.     

Structural vulnerability of the French swine industry trade network to the spread of infectious diseases

The networks generated by live animal movements are the principal vector for the propagation of infectious agents between farms, and their topology strongly affects how fast a disease may spread. The structural characteristics of networks may thus provide indicators of network vulnerability to the spread of infectious disease. This study applied social network analysis methods to describe the French swine trade network. Initial analysis involved calculating several parameters to characterize networks and then identifying high-risk subgroups of holdings for different time scales. Holding-specific centrality measurements (‘degree’, ‘betweenness’ and ‘ingoing infection chain’), which summarize the place and the role of holdings in the network, were compared according to the production type. In addition, network components and communities, areas where connectedness is particularly high and could influence the speed and the extent of a disease, were identified and analysed. Dealer holdings stood out because of their high centrality values suggesting that these holdings may control the flow of animals in part of the network. Herds with growing units had higher values for degree and betweenness centrality, representing central positions for both spreading and receiving disease, whereas herds with finishing units had higher values for in-degree and ingoing infection chain centrality values and appeared more vulnerable with many contacts through live animal movements and thus at potentially higher risk for introduction of contagious diseases. This reflects the dynamics of the swine trade with downward movements along the production chain. But, the significant heterogeneity of farms with several production units did not reveal any particular type of production for targeting disease surveillance or control. Besides, no giant strong connected component was observed, the network being rather organized according to communities of small or medium size (<20% of network size). Because of this fragmentation, the swine trade network appeared less structurally vulnerable than ruminant trade networks. This fragmentation is explained by the hierarchical structure, which thus limits the structural vulnerability of the global trade network. However, inside communities, the hierarchical structure of the swine production system would favour the spread of an infectious agent (especially if introduced in breeding herds).     

猪流行性腹泻病毒(PEDV)与抗病毒天然免疫

猪流行性腹泻病毒(porcine epidemic diarrhea virus,PEDV)是引起猪流行性腹泻病等肠道疾病的一种动物冠状病毒.PEDV与宿主系统相互作用,特别是其对宿主抗病毒天然免疫调节作用和机制是目前动物冠状病毒研究的基础科学问题之一.基于作者近几年来对人类重要冠状病毒对宿主抗病毒天然免疫系统调节作用的研究,本文对PEDV基因组与编码蛋白主要功能以及PEDV调节宿主抗病毒天然免疫反应及其可能机制的进展和现状进行了分析.与人类冠状病毒相似,PEDV编码的木瓜样蛋白酶(papain like protease,PLP)是一个多功能蛋白酶,除了蛋白酶活性外,还具有去泛素化酶(DUB)活性和宿主干扰素拮抗活性,是PEDV编码的一种新型病毒来源DUB和宿主干扰素拮抗蛋白.这些研究为阐明PEDV对宿主抗病毒天然免疫反应调节作用和其致病机制提供了重要的理论依据,为研制新型PEDV免疫防治措施提供了重要理论基础.     

Global landscape of patents related to human coronaviruses

At present, the COVID-19 pandemic is running rampant, having caused 2.18 million deaths. Characterizing the global patent landscape of coronaviruses is essential not only for informing research and policy, given the current pandemic crisis, but also for anticipating important future developments. While patents are a promising indicator of technological knowledge production widely used in innovation research, they are often an underused resource in biological sciences. In this study, we present a patent landscape for the seven coronaviruses known to infect humans. The information included in this paper provides a strong intellectual groundwork for the ongoing development of therapeutic agents and vaccines along with a deeper discussion of intellectual property rights under epidemic conditions. The results show that there has been a rapid increase in human coronavirus patents, especially COVID-19 patents. China and the United States play an outstanding role in global cooperation and patent application. The leading role of academic institutions and government is increasingly apparent. Notable technological issues related to human coronaviruses include pharmacochemical treatment, diagnosis of viral infection, viral-vector vaccines, and traditional Chinese medicine. Furthermore, a critical challenge lies in balancing commercial competition, enterprise profit, knowledge sharing, and public interest.     

Zoonotic viruses associated with illegally imported wildlife products

The global trade in wildlife has historically contributed to the emergence and spread of infectious diseases. The United States is the world's largest importer of wildlife and wildlife products, yet minimal pathogen surveillance has precluded assessment of the health risks posed by this practice. This report details the findings of a pilot project to establish surveillance methodology for zoonotic agents in confiscated wildlife products. Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP) and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. Pathogen screening identified retroviruses (simian foamy virus) and/or herpesviruses (cytomegalovirus and lymphocryptovirus) in the NHP samples. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence.     

Streamlined approach for assessing embedded consumption of lithium and cobalt in the United States

In today's complex global supply chains, time and data intensive analyses are required to understand global flows of mineral commodities from mine to consumer, particularly for mineral commodities in products (electronics, automobiles, etc.) that contain multiple parts with many mineral commodities. National and regional analyses require additional time and data to incorporate international trade flows. However, data limitations and time constraints often prohibit global and national material flow analyses for minor metals. Here we present a methodological approach to circumvent these constraints by utilizing readily available industry-level global data from the United Nations Statistics Division and national industrial data to estimate total requirements for a mineral commodity. We apply this approach to lithium and cobalt use in the United States for the year 2018 and distinguish between apparent raw material consumption versus inferred embedded consumption of lithium and cobalt materials in all forms. The results show that more than half of the United States’ total requirements for both lithium and cobalt is in parts and products that were manufactured outside the United States. In large part, this is due to limited US manufacturing capability for lithium-ion battery materials and cells and the United States’ high import reliance for electronics that use those batteries.     

猪肠道冠状病毒与入侵受体氨基肽酶N的相互作用

猪肠道冠状病毒是目前危害养猪产业的重要病原。目前已发现能够感染猪肠道的致病性冠状病毒有4种：猪传染性胃肠炎病毒、猪流行性腹泻病毒、猪丁型冠状病毒和猪肠道甲型冠状病毒。冠状病毒感染宿主的第一步是识别宿主细胞膜受体分子并与之结合,随后启动入侵及膜融合进而使病毒基因组进入宿主细胞内部。因此,冠状病毒受体是决定其宿主范围及组织嗜性的关键因素。确定冠状病毒受体及病毒与受体的结合机制对预防新发病毒及开发冠状病毒治疗性药物具有重要意义。猪传染性胃肠炎病毒利用猪氨基肽酶N（aminopeptidase N,APN）作为感染宿主的功能性受体,并利用唾液酸作为辅助结合因子。猪APN最初也被鉴定为猪流行性腹泻病毒的功能性受体,但近年的研究结果与前面的报道存在较大的差异,产生了较大的争议。最近的研究认为,猪丁型冠状病毒的功能性受体也是APN,并且猪丁型冠状病毒能够利用多个物种的APN作为功能性受体,这与其跨物种传播具有密切关系。最新发现的猪肠道甲型冠状病毒则不使用APN作为其入侵受体。本文综述了前面3种猪肠道病毒感染宿主细胞的受体及结合机制的研究进展,并比较分析了猪APN及唾液酸在不同猪肠道冠状病毒入侵宿主过程中结合方式的异同,为进一步研究新发猪肠道冠状病毒受体提供参考。     

An Evolutionary Portrait of the Progenitor SARS-CoV-2 and Its Dominant Offshoots in COVID-19 Pandemic

Global sequencing of genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to reveal new genetic variants that are the key to unraveling its early evolutionary history and tracking its global spread over time. Here we present the heretofore cryptic mutational history and spatiotemporal dynamics of SARS-CoV-2 from an analysis of thousands of high-quality genomes. We report the likely most recent common ancestor of SARS-CoV-2, reconstructed through a novel application and advancement of computational methods initially developed to infer the mutational history of tumor cells in a patient. This progenitor genome differs from genomes of the first coronaviruses sampled in China by three variants, implying that none of the earliest patients represent the index case or gave rise to all the human infections. However, multiple coronavirus infections in China and the United States harbored the progenitor genetic fingerprint in January 2020 and later, suggesting that the progenitor was spreading worldwide months before and after the first reported cases of COVID-19 in China. Mutations of the progenitor and its offshoots have produced many dominant coronavirus strains that have spread episodically over time. Fingerprinting based on common mutations reveals that the same coronavirus lineage has dominated North America for most of the pandemic in 2020. There have been multiple replacements of predominant coronavirus strains in Europe and Asia as well as continued presence of multiple high-frequency strains in Asia and North America. We have developed a continually updating dashboard of global evolution and spatiotemporal trends of SARS-CoV-2 spread (http://sars2evo.datamonkey.org/).     

The Distribution of Different Clades of Seneca Valley Viruses in Guangdong Province,China

Seneca Valley virus (SVV), a newly determined etiological agent of vesicular disease in swine, causes porcine idiopathic disease and occasional acute death in piglets. Recently, an increased number of SVV infection cases have been reported in the United States (US) and China, resulting in significant economic losses to the swine industry. The first identification of SVV in China was reported in Guangdong Province, a major swine producing province. The cases of SVV were continuously reported in Guangdong in 2015 and 2016. However, the spread of SVV in Guangdong in 2017 remains unknown.In this study, we determined two new SVV strains, CH-GD-2017-1 and CH-GD-2017-2, from Guangdong. The genetic analysis suggested that the two Guangdong strains showed different characteristics to previous Guangdong strains. They showed lower nucleotide similarity with strains isolated in 2015 and 2016, and were more similar to the US strains.Phylogenetic analyses indicated that the new strains were clustered in a different clade with previous Guangdong strains.We found 28 mutated amino acids in the new strains, compared with the first Guangdong strain, SVV CH-01-2015. In the geographic analysis, we found that the US and China reported more SVV cases than other countries, and most of the SVV cases were reported in east and central China—of which, Guangdong Province is one of the major epidemic regions. In conclusion, our findings indicate that SVV continued to spread in Guangdong Province in 2017, and two different clades of SVVs have emerged in this region.     

Evaluating the impacts of wood production and trade on bird extinction risks

Biodiversity loss can be accelerated by human consumption in regions that are far removed from habitat degradation because of economic globalization, but no study has directly quantified the effects of global trade on extinction risks at a global scale with consideration for species differences. We propose a novel biodiversity footprint index based on bird extinction risks to evaluate the effects of global wood production and trade on biodiversity. Using 536 endangered bird species threatened by wood harvesting and logging, we calculated the “quasi-extinction” probabilities, that is, the probabilities that population sizes become lower than an extinction threshold after habitat loss based on initial population sizes and forest habitat loss rates. We then used bilateral wood trade data to link the biodiversity impacts in wood exporters to wood importers. We found that if recent trends in forest cover loss continue until 2100, bird species in Brazil would be the most rapidly and heavily affected by wood production and trade, followed by those in Indonesia; these two countries alone would account for about half of all global bird extinctions. Large-scale wood importers (i.e., China, Japan, and the United States) significantly elevate overseas extinction risks and, simultaneously, reduce domestic impacts, indicating a heavy responsibility of these countries for global biodiversity loss. We also conducted a scenario analysis, which showed that the total projected number of extinct species would not decrease if each country produced the amount of wood materials necessary to meet current consumption levels. This is because bird extinction risks in tropical wood importers, such as Mexico and the Philippines, as well as Japan and China will increase if these countries increase domestic wood production. Our biodiversity footprint index is useful to identify countries whose bird species are highly affected by wood production and trade, and to quantify the role of wood trade in bird species extinctions. Additional scenario analyses are needed to establish effective patterns of wood production and consumption for bird biodiversity conservation.     

State of the art in artificial insemination of pigs in the United States.

Currently, the United States ranks second in pork production worldwide. In 1999 the breeding herd consisted of approximately 6.2 million breeding females with an annual production of 100 million market animals having an average market live weight of 118.6 kg. The objective of this paper is to briefly describe the current US swine artificial insemination (AI) industry and to profile semen production and insemination practices that are currently in use.     

Effect of Porcine Epidemic Diarrhea Virus Infectious Doses on Infection Outcomes in Na?ve Conventional Neonatal and Weaned Pigs

Porcine epidemic diarrhea virus (PEDV) was identified in the United States (U.S.) swine population for the first time in April 2013 and rapidly spread nationwide. However, no information has been published regarding the minimum infectious dose (MID) of PEDV in different pig models. The main objective of this study was to determine the oral minimum infectious dose of PEDV in naïve conventional neonatal piglets and weaned pigs. A U.S. virulent PEDV prototype isolate (USA/IN19338/2013) with known infectious titer was serially ten-fold diluted in virus-negative cell culture medium. Dilutions with theoretical infectious titers from 560 to 0.0056 TCID₅₀/ml together with a medium control were orogastrically inoculated (10ml/pig) into 7 groups of 5-day-old neonatal pigs (n = 4 per group) and 7 groups of 21-day-old weaned pigs (n = 6 per group). In 5-day-old pigs, 10ml of inoculum having titers 560–0.056 TCID₅₀/ml, corresponding to polymerase chain reaction (PCR) cycle threshold (Ct) values 24.2–37.6, resulted in 100% infection in each group; 10ml of inoculum with titer 0.0056 TCID₅₀/ml (Ct>45) caused infection in 25% of the inoculated pigs. In 21-day-old pigs, 10ml of inoculum with titers 560–5.6 TCID₅₀/ml (Ct 24.2–31.4) resulted in 100% infection in each group while 10ml of inoculum with titers 0.56–0.0056 TCID₅₀/ml (Ct values 35.3 –>45) did not establish infection in any pigs under study conditions as determined by clinical signs, PCR, histopathology, immunohistochemistry, and antibody response. These data reveal that PEDV infectious dose is age-dependent with a significantly lower MID for neonatal pigs compared to weaned pigs. This information should be taken into consideration when interpreting clinical relevance of PEDV PCR results and when designing a PEDV bioassay model. The observation of such a low MID in neonates also emphasizes the importance of strict biosecurity and thorough cleaning/disinfection on sow farms.     

Large-Scale Land Acquisition and Its Effects on the Water Balance in Investor and Host Countries

This study examines the validity of the assumption that international large-scale land acquisition (LSLA) is motivated by the desire to secure control over water resources, which is commonly referred to as ‘water grabbing’. This assumption was repeatedly expressed in recent years, ascribing the said motivation to the Gulf States in particular. However, it must be considered of hypothetical nature, as the few global studies conducted so far focused primarily on the effects of LSLA on host countries or on trade in virtual water. In this study, we analyse the effects of 475 intended or concluded land deals recorded in the Land Matrix database on the water balance in both host and investor countries. We also examine how these effects relate to water stress and how they contribute to global trade in virtual water. The analysis shows that implementation of the LSLAs in our sample would result in global water savings based on virtual water trade. At the level of individual LSLA host countries, however, water use intensity would increase, particularly in 15 sub-Saharan states. From an investor country perspective, the analysis reveals that countries often suspected of using LSLA to relieve pressure on their domestic water resources—such as China, India, and all Gulf States except Saudi Arabia—invest in agricultural activities abroad that are less water-intensive compared to their average domestic crop production. Conversely, large investor countries such as the United States, Saudi Arabia, Singapore, and Japan are disproportionately externalizing crop water consumption through their international land investments. Statistical analyses also show that host countries with abundant water resources are not per se favoured targets of LSLA. Indeed, further analysis reveals that land investments originating in water-stressed countries have only a weak tendency to target areas with a smaller water risk.     

Two amphibian diseases, chytridiomycosis and ranaviral disease, are now globally notifiable to the World Organization for Animal Health (OIE): an assessment

The global trade in amphibians entails the transport of tens of millions of live animals each year. In addition to the impact harvesting wild animals can have on amphibian populations, there is mounting evidence that the emerging pathogens Batrachochytrium dendrobatidis and ranaviruses, the aetiological agents of chytridiomycosis and ranaviral disease, respectively, are spread through this trade. The link between these pathogens and amphibian declines and extinctions suggests that the epidemiological impact of the trade is significant and may negatively affect conservation and trade economics. Here we present a brief assessment of the volume of the global trade in live amphibians, the risk of individuals harboring infection, and information on the recent listing by the World Organization for Animal Health (OIE) of chytridiomycosis and ranaviral disease in the OIE Aquatic Animal Health Code. This listing made chytridiomycosis and ranaviral disease internationally notifiable diseases and thus subject to OIE standards, which aim to assure the sanitary safety of international trade in live amphibians and their products.     

猪流行性腹泻病毒与宿主抗病毒天然免疫抑制

猪流行性腹泻病毒(porcine epidemic diarrhea virus,PEDV)能引起猪腹泻等肠道疾病,属于α属冠状病毒,它的爆发给很多国家养猪业造成了严重的经济损失。2010年以来,PEDV感染在中国出现大规模爆发,一种突变型PEDV也于2013年在美国出现并迅速传播。 RNA病毒能够通过Toll样受体通路3（TLR3）和RIG-I样受体通路（RLR）诱导I型干扰素的产生。但以往的研究表明,PEDV感染能抑制I型干扰素的合成。近年来有关PEDV调节宿主天然免疫应答的研究取得了很大进展。PEDV主要通过编码作为干扰素拮抗剂的病毒蛋白以及隐藏病毒自身病原相关分子模式（PAMP）等两种方式逃逸宿主天然免疫应答。目前已报道,PEDV非结构蛋白1可通过降解CBP阻碍干扰素调节因子3(IRF-3)组装成增强子复合体;木瓜蛋白酶样蛋白酶可通过其去泛素化酶活性阻断天然免疫信号通路传递;3C样蛋白酶可通过剪切NEMO发挥干扰素拮抗剂活性;核衣壳蛋白通过结合TBK1抑制I型干扰素产生。PEDV也可通过合成加帽酶隐藏其病原相关分子dsRNA来避免激活天然免疫通路。PEDV抗病毒天然免疫机制阐明为研究PEDV感染免疫和致病机制提供了重要的理论依据,为研发抗PEDV新型疫苗和药物提供了基础。     

Coronaviruses: emerging and re-emerging pathogens in humans and animals

The severe acute respiratory syndrome coronavirus (SARS-CoV) and recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) epidemics have proven the ability of coronaviruses to cross species barrier and emerge rapidly in humans. Other coronaviruses such as porcine epidemic diarrhea virus (PEDV) are also known to cause major disease epidemics in animals wiith huge economic loss. This special issue in Virology Journal aims to highlight the advances and key discoveries in the animal origin, viral evolution, epidemiology, diagnostics and pathogenesis of the emerging and re-emerging coronaviruses in both humans and animals.     

Identification and Risk Assessment for Worldwide Invasion and Spread of Tuta absoluta with a Focus on Sub-Saharan Africa: Implications for Phytosanitary Measures and Management

To support management decisions, molecular characterization of data and geo-reference of incidence records of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) were combined with data on the biology and ecology of the pest to estimate its climatic suitability and potential spread at regional and global scale. A CLIMEX model was developed and used for the global prediction of current and future climate-induced changes in the distributional shifts of T. absoluta. Results revealed that temperature and moisture characterized T. absoluta population growth while the pest ability to survive the cold, hot, wet and dry stress conditions are the primary characteristics defining its range frontiers. Simulated irrigation also played an important role in the model optimization. Model predictions suggest that T. absoluta represents an important threat to Africa, Asia, Australia, Northern Europe, New Zealand, Russian Federation and the United States of America (USA). Under climate change context, future predictions on distribution of T. absoluta indicated that the invasive nature of this pest will result in significant crop losses in certain locations whereas some parts of Africa may witness diminution in ranges. The following scenarios may occur: 1) T. absoluta damage potential may upsurge moderately in areas of Africa where the pest currently exists; 2) a range diminution in temperate to Sahel region with moderate upsurge in damage potential; 3) a range expansion in tropical Africa with reasonable upsurge of damage potential. These possible outcomes could be explained by the fact that the continent is already warm, with the average temperature in majority of localities near the threshold temperatures for optimal development and survival of T. absoluta. Outputs from this study should be useful in helping decision-makers in their assessment of site-specific risks of invasion and spread of T. absoluta with a view to developing appropriate surveillance, phytosanitary measures and management strategies.