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1.
Front Nutr ; 9: 870680, 2022.
Article in English | MEDLINE | ID: covidwho-1775731

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus that causes acute inflammation and severe diarrhea in newborn piglets with a high mortality rate. Given that cholesterol is required for coronavirus infection in vitro, the role of endogenous cholesterol metabolism in regulating coronavirus infection and the mechanism behind it ought to be elucidated. In this study, we found that the levels of cholesterol and bile acids were both elevated in the livers of PEDV-infected piglets compared to those of the control group. Consistently, in the livers of PEDV-infected piglets, the expression of key genes involved in cholesterol metabolism was significantly increased. Transcriptomic analysis indicated that the cholesterol homeostasis pathway was among the most enriched pathways in the livers of PEDV-infected piglets. Unexpectedly, the expression of key genes in the cholesterol metabolic pathway was downregulated at the messenger RNA (mRNA) level, but upregulated at the protein level. While the primary transcriptional factors (TFs) of cholesterol metabolism, including SREBP2 and FXR, were upregulated at both mRNA and protein levels in response to PEDV infection. Further Chromatin Immunoprecipitation Quantitative Real-time PCR (ChIP-qPCR) analysis demonstrated that the binding of these TFs to the locus of key genes in the cholesterol metabolic pathway was remarkably inhibited by PEDV infection. It was also observed that the occupancies of histone H3K27ac and H3K4me1, at the locus of the cholesterol metabolic genes HMGCR and HMGCS1, in the livers of PEDV-infected piglets, were suppressed. Together, the PEDV triggers an aberrant regulation of cholesterol metabolic genes via epigenetic inhibition of SREBP2/FXR-mediated transcription, which provides a novel antiviral target against PEDV and other coronaviruses.

2.
Front Microbiol ; 13: 865336, 2022.
Article in English | MEDLINE | ID: covidwho-1775717

ABSTRACT

A reliable and reproducible model in vitro for swine enteric coronaviruses infection would be intestinal models that support virus replication and can be long-term cultured and manipulated experimentally. Here, we designed a robust long-term culture system for porcine intestinal organoids from the intestinal crypt or single LGR5+ stem cell by combining previously defined insights into the growth requirements of the intestinal epithelium of humans. We showed that long-term cultured swine intestinal organoids were expanded in vitro for more than 6 months and maintained the potential to differentiate into different types of cells. These organoids were successfully infected with porcine enteric coronavirus, including porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV), and were capable of supporting virus replication and progeny release. RNA-seq analysis showed robust induction of transcripts associated with antiviral signaling in response to enteric coronavirus infection, including hundreds of interferon-stimulated genes and cytokines. Moreover, gene set enrichment analysis indicated that PEDV infection could suppress the immune response in organoids. This 3D intestinal organoid model offers a long-term, renewable resource for investigating porcine intestinal infections with various pathogens.

3.
Res Sq ; 2022 Mar 17.
Article in English | MEDLINE | ID: covidwho-1766250

ABSTRACT

The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. Conversely, NSP9 inhibits host gene expression by blocking mRNA export and dampens cytokine productions, including interleukin-1α/ß. Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310329

ABSTRACT

Background: To measure the public’s awareness of COVID-19 and evaluate the adequacy of public health communications and health propaganda on the prevention of coronavirus disease in Jiangsu province. Methods: : We made an electronic questionnaire and launched the survey during February 12 to March 12, 2020. Respondents were randomly selected and recruited from thirteen cities in Jiangsu province. An opportunistic sampling approach was also used to recruit new participants or members in the same household through referrals from existing participants. Data was collected through the “Questionnaire Star” system. SPSS24.0 version was used for data statistical analysis. Result: : The effective response rate of completing questionnaire was 97.14% (2650/2728). Compared with traditional media such as TV (51.43%) and newspaper (14.91%), participants were more willing to choose new media such as websites (71.17%) and social platforms such as We-Chat (73.96%) to obtained health information. Chi-square test showed that women (54.14% vs. 48.49%), the 20-50 age group (24.22% vs. 22.94%, 32.69% vs. 31.40%, 28.92 vs. 27.77%) and urban residents (61.42% vs. 59.85%) had higher COVID-19 preventive knowledge level, urban residents had better attitude (60.29% vs. 59.85%), women (53.53% vs. 51.51%), the 30-50 age group (33.14% vs. 31.40%, 29.00% vs. 27.77%)), urban residents (61.50% vs. 59.85%) had good behavior. Multivariate logistic analysis showed that gender (females vs. males, OR=2.226, OR 95%CI: 1.346-3.682, P<0.001), age groups (<50 vs. >50 years old: OR=0.689, OR 95%CI: 0.561-0.847, P<0.001), areas (urban vs. suburban: OR=0.359, OR 95%CI: 0.219-0.588, P<0.001), knowledge level (high vs. low: OR=1.259: OR 95%CI: 1.188-1.335, P<0.001), and attitude (good vs. bad: OR=0.462 OR 95%CI: 0.342-0.626, P<0.001) were associated with good behaviors. The moderating effect and mediating effect shows that attitude mediates the influence of knowledge on behavior. (The 95% interval does not include the number 0(OR95% CI:0.002-0.013). All means of health propaganda can modulate the influence between knowledge and behavior (P<0.001). Conclusions: : Providing adequacy of health propaganda and public health communications on the prevention of coronavirus disease makes the public fully understand the knowledge of COVID-19 and lead them to take preventive actions.

5.
Front Microbiol ; 12: 820698, 2021.
Article in English | MEDLINE | ID: covidwho-1686502

ABSTRACT

Rapid and sensitive nucleic acid detection of SARS-CoV-2 has contributed to the clinical diagnosis and control of COVID-19. Although detection of virus genomic RNA (gRNA) has been commonly used in clinical diagnosis, SARS-CoV-2 gRNA detection could not discriminate between active infectious virus with remnant viral RNA. In contrast to genomic RNA, subgenomic RNAs (sgRNAs) are only produced when the virus is actively replicating and transcription, detection of sgRNA could be an indication to evaluate infectivity. CRISPR/Cas-based nucleic acid detection methods have been considered potential diagnostic tools due to their intrinsic sensitivity, specificity and simplicity. In this study, to specifically detect active virus replication, we developed a CRISPR-based active SARS-CoV-2 (CRISPR-actCoV) detection strategy by detecting sgRNAs of SARS-CoV-2. CRISPR-actCoV with CRISPR Cas12a-assisted fluorescence reporter system enables detection of sgRNAs at 10 copies in 35 min with high specificity and can be read out with naked eyes. Further, we performed CRISPR-actCoV mediated sgRNA detection in 30 SARS-CoV-2 potentially infected clinical samples, and 21 samples were SARS-CoV-2 sgRNA positive. A quantitative RT-PCR assay was also performed to detect gRNA of SARS-CoV-2 in parallel. Among the 30 clinical samples, 27 samples were gRNA positive. Taken together, CRISPR-actCoV provides an alternative for rapid and accurate detection of active SARS-CoV-2 and has great significance in better response of coronavirus causing epidemic disease.

6.
Transfusion ; 61(5): 1542-1550, 2021 05.
Article in English | MEDLINE | ID: covidwho-1096956

ABSTRACT

BACKGROUND: The COVID-19 pandemic has placed additional stressors on physician lives. In this study, we report findings from a survey conducted among attending physician (AP) members of the American Society for Apheresis (ASFA) to elucidate the status of their well-being during the COVID-19 pandemic as well as resources provided or actions taken by their institutions and themselves personally to maintain or improve their well-being. STUDY DESIGN AND METHODS: A 17-question, voluntary, IRB-approved survey regarding well-being was distributed to the ASFA AP members between August 26, 2020 and September 16, 2020. The descriptive analyses were reported as number and frequency of respondents for each question. Non-parametric chi-square tests, ANOVA, and paired t-tests were performed to determine differences in categorical variables, changes in well-being scores, and compare time points, respectively. RESULTS: Based on the responses of 70 attending level physicians representing the United States (U.S., 53, 75.7%) and outside the U.S. (17, 24.3%), the following were observed: (1) COVID-19 negatively affects the well-being of a sub-population of APs, (2) neither institutional nor individual measures to improve well-being completely resolved the problem of decreased AP well-being during the pandemic, and (3) personal actions may be superior to institutional resources. CONCLUSION: There is a widespread decline in AP well-being during the COVID-19 pandemic that was not adequately improved by institutional or personal resources/actions taken. Institutions and physicians must work together to implement strategies including resources and actions that could further improve AP physician well-being during a public health crisis.


Subject(s)
Blood Component Removal , COVID-19/epidemiology , Pandemics , Physicians , Public Health , SARS-CoV-2 , Surveys and Questionnaires , Adult , Female , Humans , Male , United States/epidemiology
7.
J Clin Apher ; 35(5): 460-468, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1064369

ABSTRACT

The wide spread availability and use of sophisticated high-speed telecommunication networks coupled with inexpensive and easily accessible computing capacity have catalyzed the creation of new tools and strategies for healthcare delivery. Such tools and strategies are of value to apheresis medicine (AM) practitioners if they improve delivery of patient care, enhance safety during a therapeutic apheresis (TA) intervention, facilitate care access, advance technical capabilities of apheresis devices, and/or elevate quality performance within TA programs. In the past several years, healthcare delivery systems' adoption of telecommunication technologies has been fostered by organizational financial and quality improvement objectives. More recently, adoption of telehealth technologies has been catalyzed by the COVID-19 pandemic as these technologies enhance both patient and provider safety in an era of social distancing. These changes will also influence the delivery of TA services which now can be generally viewed in a tripartite model format comprised of traditional hospital-based fixed site locales, mobile TA operations and lately an evolving telemedicine remote management model now reffered to as telapheresis (TLA). This communication developed by the Public Affairs and Advocacy Committee of the American Society for Apheresis (ASFA) and endorsed by its Board of Directors, reviews and describes various aspects of established and evolving electronic technologies related to TLA and the practice of AM. In subsequent companion publications, additional aspects to TLA will be explored and ASFA's vision of reasonable, regulatory compliant and high-quality TLA practices will be expounded.


Subject(s)
Blood Component Removal/methods , COVID-19/epidemiology , SARS-CoV-2 , Telemedicine/methods , Humans , Mobile Health Units , Societies, Medical
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