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1.
J Biol Chem ; 298(8): 102190, 2022 Jun 24.
Article in English | MEDLINE | ID: covidwho-2015572

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) causes diarrhea and dehydration in pigs and leads to great economic losses in the commercial swine industry. However, the underlying molecular mechanisms of host response to viral infection remain unclear. In the present study, we investigated a novel mechanism by which RALY, a member of the heterogeneous nuclear ribonucleoprotein family, significantly promotes the degradation of the PEDV nucleocapsid (N) protein to inhibit viral replication. Furthermore, we identified an interaction between RALY and the E3 ubiquitin ligase MARCH8 (membrane-associated RING-CH 8), as well as the cargo receptor NDP52 (nuclear dot protein 52 kDa), suggesting that RALY could suppress PEDV replication by degrading the viral N protein through a RALY-MARCH8-NDP52-autophagosome pathway. Collectively, these results suggest a preventive role of RALY against PEDV infection via the autophagy pathway and open up the possibility of inducing RALY in vivo as an effective prophylactic and preventive treatment for PEDV infection.

2.
Epilepsy Behav ; 134: 108744, 2022 May 17.
Article in English | MEDLINE | ID: covidwho-1984253

ABSTRACT

AIM: There is a high demand for information on COVID-19 vaccination for patients with childhood epilepsy with centrotemporal spikes (BECTS). Patients with this condition need a stable, daily life; unfortunately, the decision of vaccination is not easy for their parents. We evaluated patients with BECTS for symptoms and seizure control after COVID-19 vaccination. METHODS: We asked the caregivers of all patients who visited our hospital to report their vaccination status, and if vaccinated, their experience in terms of adverse effects and seizure control after the second dose of the four Chinese-approved COVID-19 vaccines. RESULTS: Seventy-seven children had received their second COVID-19 vaccine dose: 58 of 77 (75.3%) received Sinopharm (Beijing): BBIBP-CorV (Vero cells) and 16 (20.8%) received CanSino: Ad5-nCoV. Twenty of seventy-seven (25.97%) patients with BECTS reported having side effects; all effects were mild that could be relieved themselves. For Sinopharm (Beijing): BBIBP-CorV (Vero cells), the most frequent local side effect reported by the parents was pain at the site of injection (17.24%) and systematic side effect was fatigue (15.52%). For CanSino: Ad5-nCoV, the most reported local side effect was pain at the site of injection (6.25%). All parents reported that their child's side effects could be relieved by themselves. No patient reported status epilepticus or exacerbation of a pre-existing condition. If non-vaccinated, the cause of hesitation was explored: 40% of parents worried about inducing seizures, 19% of parents worried about vaccine side effects, 32% of parents worried about the vaccine-antiepileptic drug interactions, and 9% of parents feared for their child's physical condition. More than 34.1% of parents accepted that the decision to get the vaccine for their child was difficult. Over 90% of parents believe that research on the safety and tolerability of vaccination would help them to make the decision. CONCLUSION: Our data suggest that COVID-19 vaccination is well tolerated and safe in patients below 18 years of age having BECTS, thereby supporting the recommendation of vaccination.

3.
J Virol ; 96(13): e0061822, 2022 07 13.
Article in English | MEDLINE | ID: covidwho-1962091

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) is the globally distributed alphacoronavirus that can cause lethal watery diarrhea in piglets, causing substantial economic damage. However, the current commercial vaccines cannot effectively the existing diseases. Thus, it is of great necessity to identify the host antiviral factors and the mechanism by which the host immune system responds against PEDV infection required to be explored. The current work demonstrated that the host protein, the far upstream element-binding protein 3 (FUBP3), could be controlled by the transcription factor TCFL5, which could suppress PEDV replication through targeting and degrading the nucleocapsid (N) protein of the virus based on selective autophagy. For the ubiquitination of the N protein, FUBP3 was found to recruit the E3 ubiquitin ligase MARCH8/MARCHF8, which was then identified, transported to, and degraded in autolysosomes via NDP52/CALCOCO2 (cargo receptors), resulting in impaired viral proliferation. Additionally, FUBP3 was found to positively regulate type-I interferon (IFN-I) signaling and activate the IFN-I signaling pathway by interacting and increasing the expression of tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3). Collectively, this study showed a novel mechanism of FUBP3-mediated virus restriction, where FUBP3 was found to degrade the viral N protein and induce IFN-I production, aiming to hinder the replication of PEDV. IMPORTANCE PEDV refers to the alphacoronavirus that is found globally and has re-emerged recently, causing severe financial losses. In PEDV infection, the host activates various host restriction factors to maintain innate antiviral responses to suppress virus replication. Here, FUBP3 was detected as a new host restriction factor. FUBP3 was found to suppress PEDV replication via the degradation of the PEDV-encoded nucleocapsid (N) protein via E3 ubiquitin ligase MARCH8 as well as the cargo receptor NDP52/CALCOCO2. Additionally, FUBP3 upregulated the IFN-I signaling pathway by interacting with and increasing tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3) expression. This study further demonstrated that another layer of complexity could be added to the selective autophagy and innate immune response against PEDV infection are complicated.


Subject(s)
Coronavirus Infections , Interferon Type I , Nucleocapsid Proteins , Porcine epidemic diarrhea virus , Transcription Factors , Animals , Antiviral Agents , Cell Line , Chlorocebus aethiops , Coronavirus Infections/metabolism , Interferon Type I/genetics , Interferon Type I/metabolism , Nucleocapsid Proteins/metabolism , Porcine epidemic diarrhea virus/physiology , Swine , TNF Receptor-Associated Factor 3 , Transcription Factors/metabolism , Ubiquitin-Protein Ligases , Vero Cells
4.
J Virol ; 96(10): e0007022, 2022 05 25.
Article in English | MEDLINE | ID: covidwho-1832352

ABSTRACT

In global infection and serious morbidity and mortality, porcine epidemic diarrhea virus (PEDV) has been regarded as a dreadful porcine pathogen, but the existing commercial vaccines are not enough to fully protect against the epidemic strains. Therefore, it is of great necessity to feature the PEDV-host interaction and develop efficient countermeasures against viral infection. As an RNA/DNA protein, the trans-active response DNA binding protein (TARDBP) plays a variety of functions in generating and processing RNA, including transcription, splicing, transport, and mRNA stability, which have been reported to regulate viral replication. The current work aimed to detect whether and how TARDBP influences PEDV replication. Our data demonstrated that PEDV replication was significantly suppressed by TARDBP, regulated by KLF16, which targeted its promoter. We observed that through the proteasomal and autophagic degradation pathway, TARDBP inhibited PEDV replication via the binding as well as degradation of PEDV-encoded nucleocapsid (N) protein. Moreover, we found that TARDBP promoted autophagic degradation of N protein via interacting with MARCHF8, an E3 ubiquitin ligase, as well as NDP52, a cargo receptor. We also showed that TARDBP promoted host antiviral innate immune response by inducing interferon (IFN) expression through the MyD88-TRAF3-IRF3 pathway during PEDV infection. In conclusion, these data revealed a new antiviral role of TARDBP, effectively suppressing PEDV replication through degrading virus N protein via the proteasomal and autophagic degradation pathway and activating type I IFN signaling via upregulating the expression of MyD88. IMPORTANCE PEDV refers to the highly contagious enteric coronavirus that has quickly spread globally and generated substantial financial damage to the global swine industry. During virus infection, the host regulates the innate immunity and autophagy process to inhibit virus infection. However, the virus has evolved plenty of strategies with the purpose of limiting IFN-I production and autophagy processes. Here, we identified that TARDBP expression was downregulated via the transcription factor KLF16 during PEDV infection. TARDBP could inhibit PEDV replication through the combination as well as degradation of PEDV-encoded nucleocapsid (N) protein via proteasomal and autophagic degradation pathways and promoted host antiviral innate immune response by inducing IFN expression through the MyD88-TRAF3-IRF3 pathway. In sum, our data identify a novel antiviral function of TARDBP and provide a better grasp of the innate immune response and protein degradation pathway against PEDV infection.


Subject(s)
Coronavirus Infections , DNA-Binding Proteins , Interferon Type I , Porcine epidemic diarrhea virus , Virus Replication , Animals , Coronavirus Infections/veterinary , DNA-Binding Proteins/metabolism , Immunity, Innate , Interferon Regulatory Factor-3/metabolism , Interferon Type I/metabolism , Myeloid Differentiation Factor 88/metabolism , Nucleocapsid Proteins/metabolism , Porcine epidemic diarrhea virus/genetics , Porcine epidemic diarrhea virus/physiology , RNA/metabolism , Signal Transduction , Swine , TNF Receptor-Associated Factor 3/metabolism
5.
Medicine (Baltimore) ; 101(10): e28984, 2022 Mar 11.
Article in English | MEDLINE | ID: covidwho-1806709

ABSTRACT

BACKGROUND: In December 2019, a series of acute, atypical respiratory diseases was identified in Wuhan, China. The source of the illnesses was attributed to a novel coronavirus, named the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the subsequent disease it causes was named the coronavirus disease 2019 (COVID-19). Evidence from previous coronavirus outbreaks has shown that infected patients are at risk for developing psychiatric and mental health disorders, such as depression, anxiety, and sleep disturbances. METHODS: According to the retrieval strategies, randomized controlled trials on auricular points for anxiety in patients with coronavirus 2019 will be obtained from the China National Knowledge Infrastructure, WanFang Data, Chinese Scientific Journals Database, PubMed, Embase, and Cochrane Library, regardless of publication date or language. Studies will be screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool will be used to evaluate the quality of the literature. The network meta-analysis will be performed with the Markov chain Monte Carlo method and carried out with Stata 14.2 and WinBUGS 1.4.3 software. Ultimately, the quality of the evidence obtained from the results will be evaluated. RESULTS: This study will evaluate whether auricular points can effectively treat anxiety in patients with COVID-19. CONCLUSION: This study will provide evidence for whether auricular points is beneficial to the treatment of anxiety in patients with COVID-19. INPLASY REGISTRATION NUMBER: CRD42022302649.


Subject(s)
COVID-19 , Anxiety/etiology , Anxiety/psychology , Anxiety/therapy , Humans , Meta-Analysis as Topic , Research Design , SARS-CoV-2 , Systematic Reviews as Topic
6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312579

ABSTRACT

Background: There is preliminary evidence of the long-term exposure to air pollution will affect the outcome of patients with COVID-19. More information is needed about relationship between long-term exposure to air pollution and case fatality rate (CFR) of patients with COVID-19. Methods: In this study, we have collected the data of Air Quality Index (AQI), PM2.5, PM10, SO 2 , NO 2 and O 3 from 14 representative cities in China in the past 5 years, and calculated the case fatality rate of COVID-19 in the corresponding city. First, we explored correlation relationship between CFR and long-term air quality indicators. Then, we try to point out the air pollutants that affect the level of CFR and evaluated their predictive value. Results: We have observed a positive correlation between the CFR and AQI (1-year, 3-year, 5-year), PM2.5 (1-year, 3-year, 5-year), and PM10 (1-year, 3-year, 5-year). Meanwhile, AQI (3-year, 5-year) and PM2.5 (1-year, 3-year, 5-year) were significantly higher in the high CFR group. Moderate predictive value of air pollution indicator to CFR such as AQI (1-year, 3-year, 5-year), PM2.5 (1-year, 3-year, 5-year) have been found. Conclusions: Our results indicate that long-term exposure to the environment with severe air pollution is associated with CFR of COVID-19. Air pollutants such as PM2.5 may have potential ability to predict the CFR of COVID-19.

7.
Lipids Health Dis ; 20(1): 126, 2021 Oct 03.
Article in English | MEDLINE | ID: covidwho-1448237

ABSTRACT

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). At present, the COVID-19 has been prevalent worldwide for more than a year and caused more than four million deaths. Liver injury was frequently observed in patients with COVID-19. Recently, a new definition of metabolic dysfunction associated fatty liver disease (MAFLD) was proposed by a panel of international experts, and the relationship between MAFLD and COVID-19 has been actively investigated. Several previous studies indicated that the patients with MAFLD had a higher prevalence of COVID-19 and a tendency to develop severe type of respiratory infection, and others indicated that liver injury would be exacerbated in the patients with MAFLD once infected with COVID-19. The mechanism underlying the relationship between MAFLD and COVID-19 infection has not been thoroughly investigated, and recent studies indicated that multifactorial mechanisms, such as altered host angiotensin converting enzyme 2 (ACE2) receptor expression, direct viral attack, disruption of cholangiocyte function, systemic inflammatory reaction, drug-induced liver injury, hepatic ischemic and hypoxic injury, and MAFLD-related glucose and lipid metabolic disorders, might jointly contribute to both of the adverse hepatic and respiratory outcomes. In this review, we discussed the relationship between MAFLD and COVID-19 based on current available literature, and summarized the recommendations for clinical management of MAFLD patients during the pandemic of COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , Chemical and Drug Induced Liver Injury/complications , Hypoxia/complications , Liver/metabolism , Non-alcoholic Fatty Liver Disease/complications , SARS-CoV-2/pathogenicity , Age Factors , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/virology , Cytokines/genetics , Cytokines/metabolism , Dipeptides/therapeutic use , Gene Expression Regulation , Glucose/metabolism , Glycyrrhizic Acid/therapeutic use , Humans , Hypoxia/drug therapy , Hypoxia/pathology , Hypoxia/virology , Liver/drug effects , Liver/pathology , Liver/virology , Lung/drug effects , Lung/metabolism , Lung/pathology , Lung/virology , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/virology , Receptors, Virus/genetics , Receptors, Virus/metabolism , Severity of Illness Index
8.
J Med Virol ; 93(5): 2938-2946, 2021 05.
Article in English | MEDLINE | ID: covidwho-1196525

ABSTRACT

Evidence in the literature suggests that air pollution exposure affects outcomes of patients with COVID-19. However, the extent of this effect requires further investigation. This study was designed to investigate the relationship between long-term exposure to air pollution and the case fatality rate (CFR) of patients with COVID-19. The data on air quality index (AQI), PM2.5, PM10, SO2 , NO2 , and O3 from 14 major cities in China in the past 5 years (2015-2020) were collected, and the CRF of COVID-19 patients in these cities was calculated. First, we investigated the correlation between CFR and long-term air quality indicators. Second, we examined the air pollutants affecting CFR and evaluated their predictive values. We found a positive correlation between the CFR and AQI (1, 3, and 5 years), PM2.5 (1, 3, and 5 years), and PM10 (1, 3, and 5 years). Further analysis indicated the more significant correlation for both AQI (3 and 5 years) and PM2.5 (1, 3, and 5 years) with CFR, and moderate predictive values for air pollution indicators such as AQI (1, 3, and 5 years) and PM2.5 (1, 3, and 5 years) for CFR. Our results indicate that long-term exposure to severe air pollution is associated with higher CFR of COVID-19 patients. Air pollutants such as PM2.5 may assist with the prediction of CFR for COVID-19 patients.


Subject(s)
Air Pollution/adverse effects , COVID-19/mortality , Inhalation Exposure/adverse effects , Air Pollutants/adverse effects , Air Pollutants/analysis , Air Pollution/statistics & numerical data , China/epidemiology , Cities/statistics & numerical data , Humans , Inhalation Exposure/analysis , Mortality , Predictive Value of Tests , SARS-CoV-2
9.
J Med Virol ; 93(5): 2938-2946, 2021 05.
Article in English | MEDLINE | ID: covidwho-1086484

ABSTRACT

Evidence in the literature suggests that air pollution exposure affects outcomes of patients with COVID-19. However, the extent of this effect requires further investigation. This study was designed to investigate the relationship between long-term exposure to air pollution and the case fatality rate (CFR) of patients with COVID-19. The data on air quality index (AQI), PM2.5, PM10, SO2 , NO2 , and O3 from 14 major cities in China in the past 5 years (2015-2020) were collected, and the CRF of COVID-19 patients in these cities was calculated. First, we investigated the correlation between CFR and long-term air quality indicators. Second, we examined the air pollutants affecting CFR and evaluated their predictive values. We found a positive correlation between the CFR and AQI (1, 3, and 5 years), PM2.5 (1, 3, and 5 years), and PM10 (1, 3, and 5 years). Further analysis indicated the more significant correlation for both AQI (3 and 5 years) and PM2.5 (1, 3, and 5 years) with CFR, and moderate predictive values for air pollution indicators such as AQI (1, 3, and 5 years) and PM2.5 (1, 3, and 5 years) for CFR. Our results indicate that long-term exposure to severe air pollution is associated with higher CFR of COVID-19 patients. Air pollutants such as PM2.5 may assist with the prediction of CFR for COVID-19 patients.


Subject(s)
Air Pollution/adverse effects , COVID-19/mortality , Inhalation Exposure/adverse effects , Air Pollutants/adverse effects , Air Pollutants/analysis , Air Pollution/statistics & numerical data , China/epidemiology , Cities/statistics & numerical data , Humans , Inhalation Exposure/analysis , Mortality , Predictive Value of Tests , SARS-CoV-2
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