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1.
J Virol ; : e0003722, 2022 Apr 07.
Article in English | MEDLINE | ID: covidwho-1779311

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose an enormous threat to economic activity and public health worldwide. Previous studies have shown that the nonstructural protein 5 (nsp5, also called 3C-like protease) of alpha- and deltacoronaviruses cleaves Q231 of the NF-κB essential modulator (NEMO), a key kinase in the RIG-I-like receptor pathway, to inhibit type I interferon (IFN) production. In this study, we found that both SARS-CoV-2 nsp5 and SARS-CoV nsp5 cleaved NEMO at multiple sites (E152, Q205, and Q231). Notably, SARS-CoV-2 nsp5 exhibited a stronger ability to cleave NEMO than SARS-CoV nsp5. Sequence and structural alignments suggested that an S/A polymorphism at position 46 of nsp5 in SARS-CoV versus SARS-CoV-2 may be responsible for this difference. Mutagenesis experiments showed that SARS-CoV-2 nsp5 (S46A) exhibited poorer cleavage of NEMO than SARS-CoV-2 nsp5 wild type (WT), while SARS-CoV nsp5 (A46S) showed enhanced NEMO cleavage compared with the WT protein. Purified recombinant SARS-CoV-2 nsp5 WT and SARS-CoV nsp5 (A46S) proteins exhibited higher hydrolysis efficiencies than SARS-CoV-2 nsp5 (S46A) and SARS-CoV nsp5 WT proteins in vitro. Furthermore, SARS-CoV-2 nsp5 exhibited stronger inhibition of Sendai virus (SEV)-induced interferon beta (IFN-ß) production than SARS-CoV-2 nsp5 (S46A), while introduction of the A46S substitution in SARS-CoV nsp5 enhanced suppression of SEV-induced IFN-ß production. Taken together, these data show that S46 is associated with the catalytic activity and IFN antagonism by SARS-CoV-2 nsp5. IMPORTANCE The nsp5-encoded 3C-like protease is the main coronavirus protease, playing a vital role in viral replication and immune evasion by cleaving viral polyproteins and host immune-related molecules. We showed that both SARS-CoV-2 nsp5 and SARS-CoV nsp5 cleave the NEMO at multiple sites (E152, Q205, and Q231). This specificity differs from NEMO cleavage by alpha- and deltacoronaviruses, demonstrating the distinct substrate recognition of SARS-CoV-2 and SARS-CoV nsp5. Compared with SARS-CoV nsp5, SARS-CoV-2 nsp5 encodes S instead of A at position 46. This substitution is associated with stronger catalytic activity, enhanced cleavage of NEMO, and increased interferon antagonism of SARS-CoV-2 nsp5. These data provide new insights into the pathogenesis and transmission of SARS-CoV-2.

2.
Front Psychiatry ; 13: 833865, 2022.
Article in English | MEDLINE | ID: covidwho-1775799

ABSTRACT

Objective: This paper used meta-regression to analyze the heterogenous factors contributing to the prevalence rate of mental health symptoms of the general and frontline healthcare workers (HCWs) in China under the COVID-19 crisis. Method: We systematically searched PubMed, Embase, Web of Science, and Medrxiv and pooled data using random-effects meta-analyses to estimate the prevalence rates, and ran meta-regression to tease out the key sources of the heterogeneity. Results: The meta-regression results uncovered several predictors of the heterogeneity in prevalence rates among published studies, including severity (e.g., above severe vs. above moderate, p < 0.01; above moderate vs. above mild, p < 0.01), type of mental symptoms (PTSD vs. anxiety, p = 0.04), population (frontline vs. general HCWs, p < 0.01), sampling location (Wuhan vs. Non-Wuhan, p = 0.04), and study quality (p = 0.04). Conclusion: The meta-regression findings provide evidence on the factors contributing to the prevalence rate of mental health symptoms of the general and frontline healthcare workers (HCWs) to guide future research and evidence-based medicine in several specific directions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=220592, identifier: CRD42020220592.

3.
Psychiatry and Clinical Neurosciences ; 76(2):41-50, 2022.
Article in English | APA PsycInfo | ID: covidwho-1738334

ABSTRACT

Aims: The Covid-19 pandemic has had a substantial impact on the mental health of the general public and high-risk groups worldwide. Due to its proximity and close links to China, Southeast Asia was one of the first regions to be affected by the outbreak. The aim of this systematic review was to evaluate the prevalence of anxiety, depression and insomnia in the general adult population and healthcare workers (HCWs) in Southeast Asia during the course of the first year of the pandemic. Methods: Several literature databases were systemically searched for articles published up to February 2021 and two reviewers independently evaluated all relevant studies using pre-determined criteria. The prevalence rates of mental health symptoms were calculated using a random-effect meta-analysis model. Results: In total, 32 samples from 25 studies with 20 352 participants were included. Anxiety was assessed in all 25 studies and depression in 15 studies with pooled prevalence rates of 22% and 16%, respectively. Only two studies assessed insomnia, which was estimated at 19%. The prevalence of anxiety and depression was similar among frontline HCWs (18%), general HCWs (17%), and students (20%) while being noticeably higher in the general population (27%). Conclusions: This is the first systematic review to investigate the mental health impact of the Covid-19 pandemic in Southeast Asia. A considerable proportion of the general population and HCWs reported mild to moderate symptoms of anxiety and depression;the pooled prevalence rater, however, remain significantly lower than those reported in other areas such as China and Europe. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

4.
Eur J Psychotraumatol ; 13(1): 2000132, 2022.
Article in English | MEDLINE | ID: covidwho-1684418

ABSTRACT

Objective: To perform a systematic and meta-analysis on the prevalence rates of mental health symptoms including anxiety and depression during the COVID-19 pandemic in the general population in Eastern Europe, as well as three select sub-populations: students, general healthcare workers, and frontline healthcare workers. Data sources: Studies in PubMed, Embase, Web of Science, PsycINFO, and medRxiv up to 6 February 2021. Eligibility criteria and data analysis: Prevalence rates of mental health symptoms in the general population and key sub-populations during the COVID-19 pandemic in Eastern Europe. Data were pooled using a random-effects meta-analysis to estimate the prevalence rates of anxiety and depression. Results: The meta-analysis identifies and includes 21 studies and 26 independent samples in Eastern Europe. Poland (n = 4), Serbia (n = 4), Russia (n = 3), and Croatia (n = 3) had the greatest number of studies. To our knowledge, no studies have been conducted in eleven Eastern European countries including Hungary, Slovakia, and Slovenia. The pooled prevalence of anxiety in 18 studies with 22 samples was 30% (95% CI: 24-37%) pooled prevalence of depression in 18 studies with 23 samples was 27% (95% CI: 21-34%). Implications: The cumulative evidence from the meta-analysis reveals high prevalence rates of clinically significant symptoms during the COVID-19 pandemic in Eastern Europe. The findings suggest evidence of a potential mental health crisis in Eastern Europe during the ongoing COVID-19 pandemic. Our synthesis also reveals a relative lack of studies in certain Eastern European countries as well as high heterogeneities among the existing studies, calling for more effort to achieve evidence-based mental healthcare in Eastern Europe.


Objetivo: Realizar un metanálisis sistemático sobre las tasas de prevalencia de síntomas de salud mental, incluidos ansiedad y depresión durante la pandemia de COVID-19 en la población general de Europa del Este, así como en tres subpoblaciones seleccionadas: estudiantes, trabajadores sanitarios generales y trabajadores sanitarios de primera línea.Fuentes de datos: Estudios en PubMed, Embase, Web of Science, PsycINFO y medRxiv hasta el 6 de febrero de 2021.Criterios de elegibilidad y análisis de datos: Tasas de prevalencia de síntomas de salud mental en la población general y subpoblaciones claves durante la pandemia de COVID-19 en Europa del Este. Los datos se combinaron mediante un metanálisis de efectos aleatorios para estimar las tasas de prevalencia de ansiedad y depresión.Resultados: El metanálisis identifica e incluye 21 estudios y 26 muestras independientes en Europa del Este. Polonia (n = 4), Serbia (n = 4), Rusia (n = 3) y Croacia (n = 3) tuvieron el mayor número de estudios. Hasta donde sabemos, no se han realizado estudios en once países de Europa del Este, incluidos Hungría, Eslovaquia y Eslovenia. La prevalencia combinada de ansiedad en 18 estudios con 22 muestras fue de 30% (IC del 95%: 24­37%) y la prevalencia combinada de depresión en 18 estudios con 23 muestras fue de 27% (IC del 95%: 21­34%).Implicaciones: La evidencia acumulada del metanálisis revela altas tasas de prevalencia de síntomas clínicamente significativos durante la pandemia de COVID-19 en Europa del Este. Los hallazgos sugieren evidencia de una posible crisis de salud mental en Europa del Este durante la pandemia de COVID-19 en curso. Nuestra síntesis también revela una relativa falta de estudios en ciertos países de Europa del Este, así como una gran heterogeneidad entre los estudios existentes, lo que exige un mayor esfuerzo para lograr una atención de la salud mental basada en la evidencia en Europa del Este.


Subject(s)
Anxiety/etiology , COVID-19/psychology , Depression/etiology , Anxiety/epidemiology , Depression/epidemiology , Europe, Eastern/epidemiology , Health Personnel/psychology , Health Personnel/statistics & numerical data , Humans , Students/psychology , Students/statistics & numerical data
5.
European Journal of Psychotraumatology ; 12(1), 2021.
Article in English | EuropePMC | ID: covidwho-1565060

ABSTRACT

This systematic review aims to summarize the prevalence of anxiety, depression, and insomnia in the general adult population and healthcare workers (HCWs) in several key regions worldwide during the first year of the COVID pandemic. Several literature databases were systemically searched for meta-analyses published by 22 September 2021 on the prevalence rates of mental health symptoms worldwide. The prevalence rates of mental health symptoms were summarized based on 388 empirical studies with a total of 1,067,021 participants from six regions and four countries. Comparatively, Africa and South Asia had the worse overall mental health symptoms, followed by Latin America. The research effort on mental health during COVID-19 has been highly skewed in terms of the scope of countries and mental health outcomes. The mental health symptoms are highly prevalent yet differ across regions, and such evidence helps to enable prioritization of mental health assistance efforts to allocate attention and resources based on the regional differences in mental health. HIGHLIGHTS The prevalence rates of mental health symptoms were summarized from 388 studies of 1,067,021 individuals in Africa, Asia, Eastern Europe, and Latin America. Mental health symptoms under COVID-19 pandemic were worst in Africa and South Asia followed by Latin America.

6.
Eur J Psychotraumatol ; 12(1): 2001192, 2021.
Article in English | MEDLINE | ID: covidwho-1559108

ABSTRACT

This systematic review aims to summarize the prevalence of anxiety, depression, and insomnia in the general adult population and healthcare workers (HCWs) in several key regions worldwide during the first year of the COVID pandemic. Several literature databases were systemically searched for meta-analyses published by 22 September 2021 on the prevalence rates of mental health symptoms worldwide. The prevalence rates of mental health symptoms were summarized based on 388 empirical studies with a total of 1,067,021 participants from six regions and four countries. Comparatively, Africa and South Asia had the worse overall mental health symptoms, followed by Latin America. The research effort on mental health during COVID-19 has been highly skewed in terms of the scope of countries and mental health outcomes. The mental health symptoms are highly prevalent yet differ across regions, and such evidence helps to enable prioritization of mental health assistance efforts to allocate attention and resources based on the regional differences in mental health.


El objetivo de esa revisión sistemática es el de resumir la prevalencia de la ansiedad, la depresión y el insomnio, tanto en la población general adulta como en los trabajadores de salud de diferentes regiones clave alrededor del mundo durante el primer año de la pandemia por la COVID-19. Se revisaron de manera sistemática diversas bases de datos científicas buscando metaanálisis sobre la prevalencia de síntomas en salud mental alrededor del mundo, publicados hasta el 22 de setiembre del 2021. Se resumió la prevalencia de los síntomas de salud mental sobre la base de 388 estudios empíricos, comprendiendo a 1.067.021 participantes de cuatro países y de seis regiones. África y Asia meridional tuvieron, de manera general, los peores síntomas de salud mental, seguidas por Latinoamérica. El esfuerzo por realizar investigación en salud mental durante la pandemia por la COVID-19 ha estado altamente sesgado en torno a la envergadura de los países y de las medidas de resultado empleadas en salud mental. Los síntomas de salud mental son altamente prevalentes; no obstante, difieren a lo largo de diferentes regiones. Esta evidencia ayuda a permitir la priorización de los esfuerzos de atención en salud mental asignando la atención y recursos basados sobre las diferencias regionales en salud mental.


Subject(s)
COVID-19/psychology , Global Health/statistics & numerical data , Mental Disorders/epidemiology , Pandemics , Adult , Africa/epidemiology , Asia/epidemiology , Asia, Southeastern/epidemiology , COVID-19/epidemiology , China/epidemiology , Europe, Eastern/epidemiology , Health Personnel/psychology , Humans , Latin America/epidemiology , Prevalence , Spain/epidemiology
7.
Int J Environ Res Public Health ; 18(20)2021 10 10.
Article in English | MEDLINE | ID: covidwho-1463677

ABSTRACT

We aim to provide a systematic review and meta-analysis of the prevalence rates of mental health symptoms among major African populations during the COVID-19 pandemic. We include articles from PubMed, Embase, Web of Science, PsycINFO, and medRxiv between 1 February 2020 and 6 February 2021, and pooled data using random-effects meta-analyses. We identify 28 studies and 32 independent samples from 12 African countries with a total of 15,071 participants. The pooled prevalence of anxiety was 37% in 27 studies, of depression was 45% in 24 studies, and of insomnia was 28% in 9 studies. The pooled prevalence rates of anxiety, depression, and insomnia in North Africa (44%, 55%, and 31%, respectively) are higher than those in Sub-Saharan Africa (31%, 30%, and 24%, respectively). We find (a) a scarcity of studies in several African countries with a high number of COVID-19 cases; (b) high heterogeneity among the studies; (c) the extent and pattern of prevalence of mental health symptoms in Africa is high and differs from elsewhere-more African adults suffer from depression rather than anxiety and insomnia during COVID 19 compared to adult populations in other countries/regions. Hence, our findings carry crucial implications and impact future research to enable evidence-based medicine in Africa.


Subject(s)
COVID-19 , Mental Health , Adult , Anxiety/epidemiology , Depression/epidemiology , Humans , Pandemics , Prevalence , SARS-CoV-2
8.
J Virol ; 94(20)2020 09 29.
Article in English | MEDLINE | ID: covidwho-1271852

ABSTRACT

The 3C-like protease (3CLpro) of nidovirus plays an important role in viral replication and manipulation of host antiviral innate immunity, which makes it an ideal antiviral target. Here, we characterized that porcine torovirus (PToV; family Tobaniviridae, order Nidovirales) 3CLpro autocatalytically releases itself from the viral precursor protein by self-cleavage. Site-directed mutagenesis suggested that PToV 3CLpro, as a serine protease, employed His53 and Ser160 as the active-site residues. Interestingly, unlike most nidovirus 3CLpro, the P1 residue plays a less essential role in N-terminal self-cleavage of PToV 3CLpro Substituting either P1 or P4 residue of substrate alone has little discernible effect on N-terminal cleavage. Notably, replacement of the two residues together completely blocks N-terminal cleavage, suggesting that N-terminal self-cleavage of PToV 3CLpro is synergistically affected by both P1 and P4 residues. Using a cyclized luciferase-based biosensor, we systematically scanned the polyproteins for cleavage sites and identified (FXXQ↓A/S) as the main consensus sequences. Subsequent homology modeling and biochemical experiments suggested that the protease formed putative pockets S1 and S4 between the substrate. Indeed, mutants of both predicted S1 (D159A, H174A) and S4 (P62G/L185G) pockets completely lost the ability of cleavage activity of PToV 3CLpro In conclusion, the characterization of self-processing activities and substrate specificities of PToV 3CLpro will offer helpful information for the mechanism of nidovirus 3C-like proteinase's substrate specificities and the rational development of the antinidovirus drugs.IMPORTANCE Currently, the active-site residues and substrate specificities of 3C-like protease (3CLpro) differ among nidoviruses, and the detailed catalytic mechanism remains largely unknown. Here, porcine torovirus (PToV) 3CLpro cleaves 12 sites in the polyproteins, including its N- and C-terminal self-processing sites. Unlike coronaviruses and arteriviruses, PToV 3CLpro employed His53 and Ser160 as the active-site residues that recognize a glutamine (Gln) at the P1 position. Surprisingly, mutations of P1-Gln impaired the C-terminal self-processing but did not affect N-terminal self-processing. The "noncanonical" substrate specificity for its N-terminal self-processing was attributed to the phenylalanine (Phe) residue at the P4 position in the N-terminal site. Furthermore, a double glycine (neutral) substitution at the putative P4-Phe-binding residues (P62G/L185G) abolished the cleavage activity of PToV 3CLpro suggested the potential hydrophobic force between the PToV 3CLpro and P4-Phe side chains.


Subject(s)
Coronavirus 3C Proteases/metabolism , Protein Processing, Post-Translational , Proteolysis , Torovirus Infections/embryology , Torovirus/enzymology , Animals , Coronavirus 3C Proteases/genetics , HEK293 Cells , Humans , Substrate Specificity , Swine , Torovirus/genetics , Torovirus Infections/genetics
9.
Int J Ment Health Addict ; : 1-16, 2021 Jun 22.
Article in English | MEDLINE | ID: covidwho-1279482

ABSTRACT

The evidence on the predictors of mental health in the COVID-19 pandemic has revealed contradictory findings, which prevent effective screening for mental health assistance. This study aims to identify the predictors of mental health issues, specifically examining age as a nonlinear predictor. Based on a survey of 474 adults using snowball sampling under the COVID-19 pandemic during April 1th-10th, 2020, in Iran, we found that age had a curvilinear relationship with nonsomatic pain, depression, and anxiety. Specifically, it predicted pain, depression, and anxiety disorders, negatively among adults younger than 45 years, yet positively among seniors older than 70 years. Adults who were female, were unsure about their chronic diseases, or exercised less were more likely to have mental health issues. This study, being the first paper to examine age curvilinearly, suggests future research to pay more attention to nonlinear predictors of mental health disorders in the COVID-19 pandemic.

10.
Global Health ; 17(1): 32, 2021 03 29.
Article in English | MEDLINE | ID: covidwho-1158212

ABSTRACT

BACKGROUND: The recent outbreak of COVID-19 has impacted adversely upon the mental health of millions of people worldwide. Impacts on the mental health conditions and the associated predictors relating to adults in Pakistan, the fifth most populous country in the world, during the COVID-19 remain understudied. Our aim was to investigate distress, anxiety, and overall mental health and their associated predictors among Pakistani adults in this pandemic. We specifically examine mental health issues based on the distance from the epicenter, (a predictor that has revealed opposing evidence in other countries) based on the theories of typhoon eye effect and ripple effect. The sample consisted of 601 adults who were surveyed online about 2.5 months into the outbreak across Pakistan with varying distances from the epicenter of COVID-19 of Karachi. RESULTS: The results showed that 9.2 and 19.0% of the participants surpassed the cut-off criteria for distress and anxiety disorders, respectively. Overall, the distance from the epicenter positively predicted the mental health of adults in Pakistan, and family size negatively moderated this effect. The distance from the epicenter negatively predicted distress and anxiety disorders for adults in large families, which are quite common in Pakistan. CONCLUSION: The evidence of the study interestingly finds that the prediction of the mental health of people by their distance from the epicenter depends on family size. The evidence of this study can help to provide initial indicators for mental health care providers to screen vulnerable groups in Pakistan, a populous country that continues struggling to cope with the COVID-19 pandemic.


Subject(s)
Anxiety/etiology , COVID-19/psychology , Family Characteristics , Mental Disorders/etiology , Mental Health , Pandemics , Stress, Psychological/etiology , Adaptation, Psychological , Adult , Aged , Anxiety Disorders/etiology , Cyclonic Storms , Female , Humans , Male , Middle Aged , Pakistan , Risk Factors , SARS-CoV-2 , Spatial Analysis , Surveys and Questionnaires , Young Adult
11.
Int J Ment Health Addict ; : 1, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-1126582

ABSTRACT

[This corrects the article DOI: 10.1007/s11469-020-00418-6.].

12.
Int J Ment Health Addict ; 20(2): 956-965, 2022.
Article in English | MEDLINE | ID: covidwho-1030543

ABSTRACT

Healthcare workers are under such a tremendous amount of pressure during the COVID-19 pandemic that many have become concerned about their jobs and even intend to leave them. It is paramount for healthcare workers to feel satisfied with their jobs and lives during a pandemic. This study aims to examine the predictors of job satisfaction, life satisfaction, and turnover intention of healthcare workers during the COVID-19 pandemic. Between 10 and 30 April 2020, 240 healthcare workers in Bolivia completed a cross-sectional online survey, which assessed their job satisfaction, life satisfaction, and turnover intention in the ongoing COVID-19 pandemic. The results revealed that their number of office days predicted job satisfaction, life satisfaction, and turnover intention, but the relationships varied by their age. For example, healthcare workers' office days negatively predicted job satisfaction for the young (e.g., at 25 years old: b = - 0.21; 95% CI: - 0.36 to - 0.60) but positively predicted job satisfaction for the old (e.g., at 65 years old: b = 0.25; 95% CI: 0.06 to 0.44). These findings provide evidence to enable healthcare organizations to identify staff concerned about job satisfaction, life satisfaction, and turnover intention to enable early actions so that these staffs can remain motivated to fight the prolonged COVID-19 pandemic.

13.
J Virol ; 94(15)2020 07 16.
Article in English | MEDLINE | ID: covidwho-382053

ABSTRACT

Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus. The nonstructural protein nsp5, also called 3C-like protease, is responsible for processing viral polyprotein precursors in coronavirus (CoV) replication. Previous studies have shown that PDCoV nsp5 cleaves the NF-κB essential modulator and the signal transducer and activator of transcription 2 to disrupt interferon (IFN) production and signaling, respectively. Whether PDCoV nsp5 also cleaves IFN-stimulated genes (ISGs), IFN-induced antiviral effector molecules, remains unclear. In this study, we screened 14 classical ISGs and found that PDCoV nsp5 cleaved the porcine mRNA-decapping enzyme 1a (pDCP1A) through its protease activity. Similar cleavage of endogenous pDCP1A was also observed in PDCoV-infected cells. PDCoV nsp5 cleaved pDCP1A at glutamine 343 (Q343), and the cleaved pDCP1A fragments, pDCP1A1-343 and pDCP1A344-580, were unable to inhibit PDCoV infection. Mutant pDCP1A-Q343A, which resists nsp5-mediated cleavage, exhibited a stronger ability to inhibit PDCoV infection than wild-type pDCP1A. Interestingly, the Q343 cleavage site is highly conserved in DCP1A homologs from other mammalian species. Further analyses demonstrated that nsp5 encoded by seven tested CoVs that can infect human or pig also cleaved pDCP1A and human DCP1A, suggesting that DCP1A may be the common target for cleavage by nsp5 of mammalian CoVs.IMPORTANCE Interferon (IFN)-stimulated gene (ISG) induction through IFN signaling is important to create an antiviral state and usually directly inhibits virus infection. The present study first demonstrated that PDCoV nsp5 can cleave mRNA-decapping enzyme 1a (DCP1A) to attenuate its antiviral activity. Furthermore, cleaving DCP1A is a common characteristic of nsp5 proteins from different coronaviruses (CoVs), which represents a common immune evasion mechanism of CoVs. Previous evidence showed that CoV nsp5 cleaves the NF-κB essential modulator and signal transducer and activator of transcription 2. Taken together, CoV nsp5 is a potent IFN antagonist because it can simultaneously target different aspects of the host IFN system, including IFN production and signaling and effector molecules.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus/drug effects , Coronavirus/metabolism , Cysteine Endopeptidases/metabolism , Endoribonucleases/metabolism , Trans-Activators/metabolism , Viral Nonstructural Proteins/metabolism , Animals , Coronavirus 3C Proteases , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Cysteine Endopeptidases/chemistry , Exoribonucleases/metabolism , HEK293 Cells , Host-Pathogen Interactions , Humans , Immune Evasion , Interferons/metabolism , STAT2 Transcription Factor/metabolism , Signal Transduction , Swine , Swine Diseases/virology
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