•A novel swine enteric alphacoronavirus (tentatively named SeACoV) was isolated from diarrheic piglets in southern China.•SeACoV is likely antigenetically distinct from PEDV, TGEV and PDCoV.•Genomic ...and phylogenetic analysis showed that SeACoV might have originated from the bat coronavirus HKU2.•The extreme amino-terminal domain of SeACoV spike glycoprotein had an extremely high variability compared to that of HKU2.•Experimental infection study showed that SeACoV is infectious and pathogenic in newborn piglets.
Outbreaks of diarrhea in newborn piglets without detection of transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV), have been recorded in a pig farm in southern China since February 2017. Isolation and propagation of the pathogen in cell culture resulted in discovery of a novel swine enteric alphacoronavirus (tentatively named SeACoV) related to the bat coronavirus HKU2 identified in the same region a decade ago. Specific fluorescence signal was detected in Vero cells infected with SeACoV by using a positive sow serum collected in the same farm, but not by using TGEV-, PEDV- or PDCoV-specific antibody. Electron microscopy observation demonstrated that the virus particle with surface projections was 100–120nm in diameter. Complete genomic sequencing and analyses of SeACoV indicated that the extreme amino-terminal domain of the SeACoV spike (S) glycoprotein structurally similar to the domain 0 of the alphacoronavirus NL63, whereas the rest part of S structurally resembles domains B to D of the betacoronavirus. The SeACoV-S domain 0 associated with enteric tropism had an extremely high variability, harboring 75-amino-acid (aa) substitutions and a 2-aa insertion, compared to that of HKU2, which is likely responsible for the extended host range or cross-species transmission. The isolated virus was infectious in pigs when inoculated orally into 3-day-old newborn piglets, leading to clinical signs of diarrhea and fecal virus shedding. These results confirmed that it is a novel swine enteric coronavirus representing the fifth porcine coronavirus.
Developing a new strategy to improve the self‐assembly efficiency of functional assemblies in a confined space and construct hybrid functional materials is a significant and fascinating endeavor. ...Herein, we present a highly efficient strategy for achieving the supramolecular self‐assembly of well‐defined metallacages in microdroplets through continuous‐flow microfluidic devices. The high efficiency and versatility of this approach are demonstrated by the generation of five representative metallacages in different solvents containing water, DMF, acetonitrile, and methanol in a few minutes with nearly quantitative yields, in contrast to the yields obtained with the hour‐scale reaction time in a batch reactor. A ring‐opening catalytic reaction of the metallacages was selected as a model reaction for exploring supramolecular catalysis in microdroplets, whereby the catalytic yield was enhanced by 2.22‐fold compared to that of the same reaction in the batch reactor. This work illustrates a new promising approach for the self‐assembly of supramolecular systems.
Supramolecular self‐assembly of well‐defined metallacages in microdroplets was achieved through a continuous‐flow microfluidic approach. The high efficiency and diversity of this strategy were illustrated by the generation of five representative metallacages with nearly quantitative yields in a few minutes. This approach is promising for the self‐assembly of supramolecular systems in a confined space.
Intestinal microbial metabolites have been increasingly recognized as important regulators of enteric viral infection. However, very little information is available about which specific ...microbiota-derived metabolites are crucial for swine enteric coronavirus (SECoV) infection in vivo. Using swine acute diarrhea syndrome (SADS)-CoV as a model, we were able to identify a greatly altered bile acid (BA) profile in the small intestine of infected piglets by untargeted metabolomic analysis. Using a newly established ex vivo model-the stem cell-derived porcine intestinal enteroid (PIE) culture-we demonstrated that certain BAs, cholic acid (CA) in particular, enhance SADS-CoV replication by acting on PIEs at the early phase of infection. We ruled out the possibility that CA exerts an augmenting effect on viral replication through classic farnesoid X receptor or Takeda G protein-coupled receptor 5 signaling, innate immune suppression or viral attachment. BA induced multiple cellular responses including rapid changes in caveolae-mediated endocytosis, endosomal acidification and dynamics of the endosomal/lysosomal system that are critical for SADS-CoV replication. Thus, our findings shed light on how SECoVs exploit microbiome-derived metabolite BAs to swiftly establish viral infection and accelerate replication within the intestinal microenvironment.
•A summary of the research progress in SeACoV (SADS-CoV) from 2017 to 2020.•Bat-derived SeACoV was most recently recognized prior to SARS-CoV-2 associated with COVID-19.•Focusing on the etiology, ...epidemiology, evolutionary perspective, potential for interspecies transmission, pathogenesis and diagnosis.
Discovered in 2017, swine enteric alphacoronavirus (SeACoV), also known as swine acute diarrhea syndrome coronavirus (SADS-CoV) or porcine enteric alphacoronavirus (PEAV), is the fifth porcine CoV identified in diarrheal piglets. The presumed name “SADS-CoV” may not be appropriate since current studies have not provided strong evidence for high pathogenicity of the virus. SeACoV was the most recently recognized CoV of potential bat origin prior to the novel human severe acute respiratory syndrome CoV 2 (SARS-CoV-2), associated with the pandemic CoV disease 2019 (COVID-19). Although SeACoV is recognized as a regional epizootic virus currently, it possesses the most extensive cell species tropism in vitro among known CoVs. This review summarizes the emergence of SeACoV and updates the research progress made from 2017 to early 2020, mainly focusing on the etiology, epidemiology, evolutionary perspective, potential for interspecies transmission, pathogenesis and diagnosis.
Swine acute diarrhea syndrome coronavirus (SADS‐CoV) is a newly discovered alphacoronavirus with zoonotic potential that causes diarrhea and vomiting mainly in piglets. Having emerged suddenly in ...2017, the prevailing opinion is that the virus originated from HKU2, an alphacoronavirus whose primary host is bats, and at some unknown point achieved interspecies transmission via some intermediate. Here, we further explore the evolutionary history and possible cross‐species transmission event for SADS‐CoV. Coevolutionary analysis demonstrated that HKU2 may have achieved host switch via SADS‐related (SADSr)‐CoV, which was isolated from the genus Rhinolophus in 2017. SADS‐CoV, HKU2, and SADSr‐CoV share similar codon usage patterns and showed a lower tendency to use CpG, which may reflect a method of immune escape. The analyses of virus‐host coevolution and recombination support SADSr‐CoV is the direct source of SADS‐CoV that may have undergone recombination events during its formation. Structure‐based spike glycoprotein variance analysis revealed a more nuanced evolutionary pathway to receptor recognition for host switch. We did not find a possible positive selection site, and the dN/dS of the S gene was only 0.29, which indicates that the current SADS‐CoV is slowly evolving. These results provide new insights that may help predict future cross‐species transmission, and possibly surveil future zoonotic outbreaks and associated public health emergencies.
•Novel deep GSHP system using abandoned oil well was presented.•Heat supply of unit depth by the system reached to 192 kW/m.•There was an optimal inlet temperature obtaining largest system COP.•The ...order of parameters’ intensity of effect on COP was obtained.•Flow rate showed the strongest influence on the system COP.
As one of the most important geothermal applications, ground source heat pump (GSHP) systems have been applied for spacing heating and cooling of buildings, and the abandoned oil wells (AOW) with deep depth contain abundant geothermal energy. Therefore, this study proposed a new GSHP system using single AOW, and the deep coaxial borehole heat exchanger (BHE) with insulation is introduced to retrofit the wellbore of AOW for heat extraction. At first, a comprehensive heat transfer model for the deep coaxial BHE combing fluid, borehole and ground was built to evaluate the performance of the proposed GSHP systems during annual run. Then, Monte Carlo method was used for parameters sensitivity analysis to obtain the PRCC determining the intensity of parameters effect on total system COP. Lastly, the optimization of injection parameters was performed. The results indicated that flow rate showed the strongest influence on the total system COP. During the annual operation, it was found that the mean heat supply by the AOW-GSHP system was about 384 kW, and reached to 192 kW/m for unit depth which was obviously higher than that in conventional GSHP. And the mean heat extraction from AOW by the AOW-GSHP system reached to 294 kW, more than that by directing heating using AOW. By the optimization, it was found there was optimal inlet temperature getting maximum system COP and it existed a minimum injection pressure supporting system operation.
Direct myocardial and vascular injuries due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven inflammation is the leading cause of acute cardiac injury associated with ...coronavirus disease 2019 (COVID-19). However, in-depth knowledge of the injury characteristics of the heart affected by inflammation is lacking. In this study, using a quantitative spatial proteomics strategy that combines comparative anatomy, laser-capture microdissection, and histological examination, we establish a region-resolved proteome map of the myocardia and microvessels with obvious inflammatory cells from hearts of patients with COVID-19. A series of molecular dysfunctions of myocardia and microvessels is observed in different cardiac regions. The myocardia and microvessels of the left atrial are the most susceptible to virus infection and inflammatory storm, suggesting more attention should be paid to the lesion and treatment of these two parts. These results can guide in improving clinical treatments for cardiovascular diseases associated with COVID-19.
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•Spatial proteome maps of COVID-19 myocardia and microvessels are established•SARS-CoV-2-driven inflammation leads to region-resolved dysfunction of the heart•Mechanisms of dysregulated contraction, conduction, and circulation are elaborated•Myocardia and microvessels of the left atrium are affected by inflammation the most
Leng et al. establish a region-resolved proteome map of the inflammatory myocardia and microvessels of COVID-19 hearts. The myocardia and microvessels of the left atrium are the most affected by inflammation storm. These results could provide guidance in improvement of clinical treatments for cardiovascular diseases associated with COVID-19.
Outbreaks of severe diarrhea in neonatal piglets in Guangdong, China, in 2017 resulted in the isolation and discovery of a novel swine enteric alphacoronavirus (SeACoV) derived from the species
(Y. ...Pan, X. Tian, P. Qin, B. Wang, et al., Vet Microbiol 211:15-21, 2017). SeACoV was later referred to as swine acute diarrhea syndrome CoV (SADS-CoV) by another group (P. Zhou, H. Fan, T. Lan, X.-L. Yang, et al., Nature 556:255-258, 2018). The present study was set up to investigate the potential species barriers of SADS-CoV
and
We first demonstrated that SADS-CoV possesses a broad species tropism and is able to infect cell lines from diverse species, including bats, mice, rats, gerbils, hamsters, pigs, chickens, nonhuman primates, and humans. Trypsin contributes to but is not essential for SADS-CoV propagation
Furthermore, C57BL/6J mice were inoculated with the virus via oral or intraperitoneal routes. Although the mice exhibited only subclinical infection, they supported viral replication and prolonged infection in the spleen. SADS-CoV nonstructural proteins and double-stranded RNA were detected in splenocytes of the marginal zone on the edge of lymphatic follicles, indicating active replication of SADS-CoV in the mouse model. We identified that splenic dendritic cells (DCs) are the major targets of virus infection by immunofluorescence and flow cytometry approaches. Finally, we demonstrated that SADS-CoV does not utilize known CoV receptors for cellular entry. The ability of SADS-CoV to replicate in various cells lines from a broad range of species and the unexpected tropism for murine DCs provide important insights into the biology of this bat-origin CoV, highlighting its possible ability to cross interspecies barriers.
Infections with bat-origin coronaviruses (CoVs) (severe acute respiratory syndrome CoV SARS-CoV and Middle East respiratory syndrome CoV MERS-CoV) have caused severe illness in humans after "host jump" events. Recently, a novel bat-HKU2-like CoV named swine acute diarrhea syndrome CoV (SADS-CoV) has emerged in southern China, causing lethal diarrhea in newborn piglets. It is important to assess the species barriers of SADS-CoV infection since the animal hosts (other than pigs and bats) and zoonotic potential are still unknown. An
susceptibility study revealed a broad species tropism of SADS-CoV, including various rodent and human cell lines. We established a mouse model of SADS-CoV infection, identifying its active replication in splenic dendritic cells, which suggests that SADS-CoV has the potential to infect rodents. These findings highlight the potential cross-species transmissibility of SADS-CoV, although further surveillance in other animal populations is needed to fully understand the ecology of this bat-HKU2-origin CoV.
A PEDV/PDCoV/TGEV/SADS-CoV/XIPC 5-plex real-time RT-PCR was developed and validated for the simultaneous detection and differentiation of four swine enteric coronaviruses (PEDV, PDCoV, TGEV and ...SADS-CoV) in one PCR reaction (XIPC serves as an exogenous internal positive control). The 5-plex PCR had excellent analytical specificity, analytical sensitivity, and repeatability based on the testing of various viral and bacterial pathogens, serial dilutions of virus isolates, and in vitro transcribed RNAs. The 5-plex PCR had comparable diagnostic performance to a commercial PEDV/TGEV/PDCoV reference PCR, based on the testing of 219 clinical samples. Subsequently, 1807 clinical samples collected from various U.S. states during 2019–2021 were tested by the 5-plex PCR to investigate the presence of SADS-CoV in U.S. swine and the frequency of detecting swine enteric CoVs. All 1807 samples tested negative for SADS-CoV. Among the samples positive for swine enteric CoVs, there was a low frequency of detecting TGEV, an intermediate frequency of detecting PDCoV, and a high frequency of detecting PEDV. Although there is no evidence of SADS-CoV presence in the U.S. at present, the availability of the 5-plex PCR will enable us to conduct ongoing surveillance to detect and differentiate these viruses in swine samples and other host species samples as some of these coronaviruses can cause cross-species infection.
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