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1.
Front Microbiol ; 12: 752597, 2021.
Article in English | MEDLINE | ID: covidwho-1470762

ABSTRACT

Coronavirus disease 2019 (COVID-19) has caused a crisis to global public health since its outbreak at the end of 2019. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of COVID-19, appears to efficiently evade the host immune responses, including interferon (IFN) signaling. Several SARS-CoV-2 viral proteins are believed to involve in the inhibition of IFN signaling. In this study, we discovered that ORF3a, an accessory protein of SARS-CoV-2, inhibited IFN-activated Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling via upregulating suppressor of cytokine signaling 1 (SOCS1), a negative regulator of cytokine signaling. ORF3a induced SOCS1 elevation in a dose- and time-dependent manner. RNAi-mediated silencing of SOCS1 efficiently abolished ORF3a-induced blockage of JAK/STAT signaling. Interestingly, we found that ORF3a also promoted the ubiquitin-proteasomal degradation of Janus kinase 2 (JAK2), an important kinase in IFN signaling. Silencing of SOCS1 by siRNA distinctly blocked ORF3a-induced JAK2 ubiquitination and degradation. These results demonstrate that ORF3a dampens IFN signaling via upregulating SOCS1, which suppressed STAT1 phosphorylation and accelerated JAK2 ubiquitin-proteasomal degradation. Furthermore, analysis of ORF3a deletion constructs showed that the middle domain of ORF3a (amino acids 70-130) was responsible for SOCS1 upregulation. These findings contribute to our understanding of the mechanism of SARS-CoV-2 antagonizing host antiviral response.

2.
Clin Lab ; 67(9)2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1431125

ABSTRACT

BACKGROUND: Chest CT is important for the diagnosis of Corona Virus Disease 2019, which is caused by SARS-CoV-2 via the receptor angiotensin-converting enzyme 2. This study aimed to present special chest CT changes in the detection and management of COVID-19. METHODS: From February 20 to March 6, 2020, clinical data and chest CT of patients with COVID-19 being treated by the Hubei Medical Team were retrospectively analyzed with a time-interval of 2 weeks. In addition, the expressions of ACE2 in different parts of the respiratory system were detected by immunohistochemical staining to explain the special chest CT features of COVID-19 by ACE2 expression. RESULTS: Of 58 patients, the main respiratory manifestations were fever and cough. Spherical or patchy GGO was the initial CT manifestation of COVID-19 pneumonia. CT findings manifested as rapid evolution from focal unilateral to diffuse bilateral ground-glass opacities (GGO) that progressed to or co-existed with consolidations in chest CT scans. Lung consolidation increased as the disease progressed, accounting for 63.2%, 76.3%, and 87.5% in group 1 (disease course with 0 - 2 weeks), group 2 (2 - 4 weeks), and group 3 (> 4 weeks). Fibrous lesions (72.3%), high density vascular shadow (69.2%), reticular pattern (63.1%), and subpleural parallel sign (61.5%) were common signs of chest CT of COVID-19. IHC results showed that ACE2-expression in the pulmonary alveoli was significantly higher than that in the bronchial mucosa and pleura (p < 0.001). CONCLUSIONS: The special change of CT features in the lung of COVID-19 pneumonia patients have a connection with ACE2 expression patterns in the respiratory system.


Subject(s)
COVID-19 , Peptidyl-Dipeptidase A , Humans , Lung/diagnostic imaging , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
3.
Front Immunol ; 12: 653110, 2021.
Article in English | MEDLINE | ID: covidwho-1305643

ABSTRACT

To characterize transcriptomic changes in endothelial cells (ECs) infected by coronaviruses, and stimulated by DAMPs, the expressions of 1311 innate immune regulatomic genes (IGs) were examined in 28 EC microarray datasets with 7 monocyte datasets as controls. We made the following findings: The majority of IGs are upregulated in the first 12 hours post-infection (PI), and maintained until 48 hours PI in human microvascular EC infected by middle east respiratory syndrome-coronavirus (MERS-CoV) (an EC model for COVID-19). The expressions of IGs are modulated in 21 human EC transcriptomic datasets by various PAMPs/DAMPs, including LPS, LPC, shear stress, hyperlipidemia and oxLDL. Upregulation of many IGs such as nucleic acid sensors are shared between ECs infected by MERS-CoV and those stimulated by PAMPs and DAMPs. Human heart EC and mouse aortic EC express all four types of coronavirus receptors such as ANPEP, CEACAM1, ACE2, DPP4 and virus entry facilitator TMPRSS2 (heart EC); most of coronavirus replication-transcription protein complexes are expressed in HMEC, which contribute to viremia, thromboembolism, and cardiovascular comorbidities of COVID-19. ECs have novel trained immunity (TI), in which subsequent inflammation is enhanced. Upregulated proinflammatory cytokines such as TNFα, IL6, CSF1 and CSF3 and TI marker IL-32 as well as TI metabolic enzymes and epigenetic enzymes indicate TI function in HMEC infected by MERS-CoV, which may drive cytokine storms. Upregulated CSF1 and CSF3 demonstrate a novel function of ECs in promoting myelopoiesis. Mechanistically, the ER stress and ROS, together with decreased mitochondrial OXPHOS complexes, facilitate a proinflammatory response and TI. Additionally, an increase of the regulators of mitotic catastrophe cell death, apoptosis, ferroptosis, inflammasomes-driven pyroptosis in ECs infected with MERS-CoV and the upregulation of pro-thrombogenic factors increase thromboembolism potential. Finally, NRF2-suppressed ROS regulate innate immune responses, TI, thrombosis, EC inflammation and death. These transcriptomic results provide novel insights on the roles of ECs in coronavirus infections such as COVID-19, cardiovascular diseases (CVD), inflammation, transplantation, autoimmune disease and cancers.


Subject(s)
Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Endothelial Cells/physiology , Inflammation/immunology , Middle East Respiratory Syndrome Coronavirus/physiology , NF-E2-Related Factor 2/metabolism , SARS-CoV-2/physiology , Alarmins/immunology , Animals , Datasets as Topic , Endothelial Cells/virology , Gene Expression Profiling , Humans , Immunity, Innate , Immunization , Mice , Myelopoiesis , Oxidative Stress , Thromboembolism
4.
Geohealth ; 5(6): e2020GH000358, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1139710

ABSTRACT

As of July 27, 2020, COVID-19 has caused 640,000 deaths worldwide and has had a major impact on people's productivity and lives. Analyzing the spatial distribution characteristics of COVID-19 cases and their relationships with meteorological and environmental factors might help enrich our knowledge of virus transmission and formulate reasonable epidemic prevention strategies. Taking the cumulative confirmed cases in Hubei province from January 23, 2020, to April 8, 2020, as an example, this study analyzed the spatial evolution characteristics of confirmed COVID-19 cases in Hubei province using exploratory spatial data analysis and explored the spatial relationship between the main environmental and meteorological factors and confirmed COVID-19 cases using a geographically weighted regression (GWR) model. Results show that there was no obvious spatial clustering of confirmed COVID-19 cases in Hubei province, while the decline and end of the newly confirmed cases revealed relatively obvious negative spatial correlations. Due to the lockdown in Hubei province, the main air quality indexes (e.g., AQI and PM2.5) decreased significantly and environmental quality was better than historical contemporaneous levels. Meanwhile, the results of the GWR model suggest that the impacts of environmental and meteorological factors on the development of COVID-19 were not significant. These findings indicate that measures such as social distancing and isolation played the primary role in controlling the development of the COVID-19 epidemic.

5.
J Cell Mol Med ; 24(21): 12457-12463, 2020 11.
Article in English | MEDLINE | ID: covidwho-796054

ABSTRACT

Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) has rapidly spread worldwide, threatening the health and lives of many people. Unfortunately, information regarding the immunological characteristics of COVID-19 patients remains limited. Herein, we collected blood samples from 18 healthy donors (HDs) and 38 COVID-19 patients to analyse changes in the adaptive immune cell populations and their phenotypes. We observed that the lymphocyte percentage moderately decreased, CD4 and CD8 T cell percentage among lymphocytes were similar, and B cell percentage was increased in COVID-19 patients in comparison to that in HDs. T cells, especially CD8 T cells, showed an enhanced expression of late activation marker CD25 and exhaustion marker PD-1. Importantly, SARS-CoV-2 infection increased the percentage of T follicular helper- and germinal centre B-like cells in the blood. The parameters in COVID-19 patients remained unchanged across various age groups. Therefore, we demonstrated that the T and B cells are activated naturally and are functional during SARS-CoV-2 infection. These data provide evidence that the adaptive immunity in most patients could be primed to induce a significant immune response against SARS-CoV-2 infection upon receiving standard medical care.


Subject(s)
Adaptive Immunity , COVID-19/immunology , Adult , Antigens, CD/metabolism , B-Lymphocytes/virology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/virology , COVID-19/blood , Female , Humans , Immunophenotyping , Male , Programmed Cell Death 1 Receptor/metabolism , Receptors, CXCR5/metabolism
6.
IEEE Trans Ultrason Ferroelectr Freq Control ; 67(11): 2249-2257, 2020 11.
Article in English | MEDLINE | ID: covidwho-793977

ABSTRACT

Ultrasound elastography (US-E) is a noninvasive, safe, cost-effective and reliable technique to assess the mechanical properties of soft tissue and provide imaging biomarkers for pathological processes. Many lung diseases such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and interstitial lung disease are associated with dramatic changes in mechanical properties of lung tissues. Nevertheless, US-E is rarely used to image the lung because it is filled with air. The large difference in acoustic impedance between air and lung tissue results in the reflection of the ultrasound wave at the lung surface and, consequently, the loss of most ultrasound energy. In recent years, there has been an increasing interest in US-E applications in evaluating lung diseases. This article provides a comprehensive review of the technological advances of US-E research on lung disease diagnosis. We introduce the basic principles and major techniques of US-E and provide information on various applications in lung disease assessment. Finally, the potential applications of US-E to the diagnosis of COVID-19 pneumonia is discussed.


Subject(s)
Elasticity Imaging Techniques , Lung Diseases/diagnostic imaging , Lung/diagnostic imaging , Betacoronavirus , COVID-19 , Coronavirus Infections/diagnostic imaging , Humans , Pandemics , Pneumonia, Viral/diagnostic imaging , SARS-CoV-2
7.
Emerg Microbes Infect ; 9(1): 1474-1488, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-599992

ABSTRACT

The mutations in the SARS-CoV-2 virus genome during COVID-19 dissemination are unclear. In 788 COVID-19 patients from Zhejiang province, we observed decreased rate of severe/critical cases compared with patients in Wuhan. For mechanisms exploration, we isolated one strain of SARS-CoV-2 (ZJ01) from a mild COVID-19 patient. Thirty-five specific gene mutations were identified. Phylogenetic and relative synonymous codon usage analysis suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 global virus strains based on the base (C or T) at positions 8824 and 28247 while ZJ01 has T at both sites. The prediction of the Furin cleavage site (FCS) and sequence alignment indicated that the FCS may be an important site of coronavirus evolution. ZJ01 mutations identified near the FCS (F1-2) caused changes in the structure and electrostatic distribution of the S surface protein, further affecting the binding capacity of Furin. Single-cell sequencing and ACE2-Furin co-expression results confirmed that the Furin expression was especially higher in glands, liver, kidneys, and colon. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 caused mild flu-like symptoms, further showing its potential in differentiating into mild COVID-19 subtypes.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Furin/metabolism , Pneumonia, Viral/virology , Adult , Betacoronavirus/genetics , COVID-19 , China/epidemiology , Codon , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Disease Progression , Evolution, Molecular , Female , Humans , Male , Middle Aged , Mutation , Pandemics , Phylogeny , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Retrospective Studies , SARS-CoV-2 , Sequence Analysis, RNA
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