Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 10 de 10
Filter
1.
Immunity ; 54(12): 2673-2675, 2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1709840

ABSTRACT

We talk to first and last authors Katalin Karikó and Drew Weissman about their seminal 2005 paper ''Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA", about how they see the work in retrospect, the current progress in the field, and their inspiration-then and now.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , RNA/immunology , SARS-CoV-2/physiology , Toll-Like Receptors/metabolism , /immunology , Access to Information , Animals , Humans , Information Dissemination , Mice , Nucleosides/immunology
2.
Cells ; 11(3)2022 01 30.
Article in English | MEDLINE | ID: covidwho-1667057

ABSTRACT

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing, as is research on the molecular mechanisms underlying cellular infection by coronaviruses, with the hope of developing therapeutic agents against this pandemic. Other important respiratory viruses such as 2009 pandemic H1N1 and H7N9 avian influenza virus (AIV), influenza A viruses, are also responsible for a possible outbreak due to their respiratory susceptibility. However, the interaction of these viruses with host cells and the regulation of post-transcriptional genes remains unclear. In this study, we detected and analyzed the comparative transcriptome profiling of SARS-CoV-2, panH1N1 (A/California/07/2009), and H7N9 (A/Shanghai/1/2013) infected cells. The results showed that the commonly upregulated genes among the three groups were mainly involved in autophagy, pertussis, and tuberculosis, which indicated that autophagy plays an important role in viral pathogenicity. There are three groups of commonly downregulated genes involved in metabolic pathways. Notably, unlike panH1N1 and H7N9, SARS-CoV-2 infection can inhibit the m-TOR pathway and activate the p53 signaling pathway, which may be responsible for unique autophagy induction and cell apoptosis. Particularly, upregulated expression of IRF1 was found in SARS-CoV-2, panH1N1, and H7N9 infection. Further analysis showed SARS-CoV-2, panH1N1, and H7N9 infection-induced upregulation of lncRNA-34087.27 could serve as a competitive endogenous RNA to stabilize IRF1 mRNA by competitively binding with miR-302b-3p. This study provides new insights into the molecular mechanisms of influenza A virus and SARS-CoV-2 infection.


Subject(s)
COVID-19/immunology , Immunity/immunology , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H7N9 Subtype/immunology , Influenza, Human/immunology , RNA/immunology , Transcriptome/immunology , A549 Cells , Animals , COVID-19/genetics , COVID-19/virology , HEK293 Cells , Host-Pathogen Interactions/immunology , Humans , Immunity/genetics , Influenza A Virus, H1N1 Subtype/physiology , Influenza A Virus, H7N9 Subtype/physiology , Influenza, Human/genetics , Influenza, Human/virology , Interferon Regulatory Factor-1/genetics , Interferon Regulatory Factor-1/immunology , Interferon Regulatory Factor-1/metabolism , MicroRNAs/genetics , MicroRNAs/immunology , MicroRNAs/metabolism , Pandemics/prevention & control , RNA/genetics , RNA/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/immunology , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , RNA, Messenger/immunology , RNA, Messenger/metabolism , RNA-Seq/methods , SARS-CoV-2/physiology , Signal Transduction/genetics , Signal Transduction/immunology , Transcriptome/genetics
3.
Proc Natl Acad Sci U S A ; 118(46)2021 11 16.
Article in English | MEDLINE | ID: covidwho-1504541

ABSTRACT

A chance conversation with a nonscientist about the mRNA-COVID vaccines, conveyed here, reminded the author of our enduring responsibility to accurately portray science to the public.


Subject(s)
RNA/genetics , RNA/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Humans , RNA, Messenger/genetics , RNA, Messenger/immunology , SARS-CoV-2/immunology
4.
Nanomedicine ; 37: 102438, 2021 10.
Article in English | MEDLINE | ID: covidwho-1306447

ABSTRACT

Highly pathogenic avian influenza viruses (HPAIVs) pose a significant threat to human health, with high mortality rates, and require effective vaccines. We showed that, harnessed with novel RNA-mediated chaperone function, hemagglutinin (HA) of H5N1 HPAIV could be displayed as an immunologically relevant conformation on self-assembled chimeric nanoparticles (cNP). A tri-partite monomeric antigen was designed including: i) an RNA-interaction domain (RID) as a docking tag for RNA to enable chaperna function (chaperna: chaperone + RNA), ii) globular head domain (gd) of HA as a target antigen, and iii) ferritin as a scaffold for 24 mer-assembly. The immunization of mice with the nanoparticles (~46 nm) induced a 25-30 fold higher neutralizing capacity of the antibody and provided cross-protection from homologous and heterologous lethal challenges. This study suggests that cNP assembly is conducive to eliciting antibodies against the conserved region in HA, providing potent and broad protective efficacy.


Subject(s)
Hemagglutinin Glycoproteins, Influenza Virus/immunology , Influenza A Virus, H5N1 Subtype/drug effects , Influenza Vaccines/immunology , Influenza in Birds/immunology , RNA/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/immunology , Antibodies, Viral/therapeutic use , Birds/virology , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Hemagglutinin Glycoproteins, Influenza Virus/therapeutic use , Humans , Influenza A Virus, H5N1 Subtype/immunology , Influenza A Virus, H5N1 Subtype/pathogenicity , Influenza Vaccines/chemistry , Influenza Vaccines/therapeutic use , Influenza in Birds/prevention & control , Influenza in Birds/virology , Mice , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Pandemics , RNA/genetics , RNA/therapeutic use
5.
Chem Biol Interact ; 344: 109497, 2021 Aug 01.
Article in English | MEDLINE | ID: covidwho-1312959

ABSTRACT

Extracellular vesicles like exosomes are important therapeutic tactics for treating COVID -19. By utilizing convalescent plasma derived exosomes (CPExo) from COVID-19 recovered persistence could accelerate the treatment strategies in the current state of affairs. Adequate literature has shown that administering the exosome to the in vivo system could be beneficial and could target the pathogens in an effective and precise manner. In this hypothesis we highlight the CPExo instead of convalescent plasma (CP), perhaps to dispense of exosomes are gratified and it's more effectively acquired immune response conferral through antibodies. COVID-19 convalescent plasma has billions of exosomes and it has aptitudes to carry molecular constituents like proteins, lipids, RNA and DNA, etc. Moreover, exosomes are capable of recognizing antigens with adequate sensitivity and specificity. Many of these derivatives could trigger an immune modulation into the cells and act as an epigenetic inheritor response to target pathogens through RNAs. COIVID-19 resistance activated plasma-derived exosomes are either responsible for the effects of plasma beyond the contained immune antibodies or could be inhibitory. The proposed hypothesis suggests that preselecting the plasma-derived antibodies and RNAs merged exosomes would be an optimized therapeutic tactic for COVID-19 patients. We suggest that, the CPExo has a multi-potential effect for treatment efficacy by acting as immunotherapeutic, drug carrier, and diagnostic target with noncoding genetic materials as a biomarker.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Exosomes/immunology , Plasma/immunology , Adaptive Immunity/immunology , Antibodies/immunology , Antigens/immunology , DNA/immunology , Humans , Immunization, Passive , RNA/immunology , SARS-CoV-2/immunology
6.
Chem Biol Interact ; 344: 109497, 2021 Aug 01.
Article in English | MEDLINE | ID: covidwho-1309180

ABSTRACT

Extracellular vesicles like exosomes are important therapeutic tactics for treating COVID -19. By utilizing convalescent plasma derived exosomes (CPExo) from COVID-19 recovered persistence could accelerate the treatment strategies in the current state of affairs. Adequate literature has shown that administering the exosome to the in vivo system could be beneficial and could target the pathogens in an effective and precise manner. In this hypothesis we highlight the CPExo instead of convalescent plasma (CP), perhaps to dispense of exosomes are gratified and it's more effectively acquired immune response conferral through antibodies. COVID-19 convalescent plasma has billions of exosomes and it has aptitudes to carry molecular constituents like proteins, lipids, RNA and DNA, etc. Moreover, exosomes are capable of recognizing antigens with adequate sensitivity and specificity. Many of these derivatives could trigger an immune modulation into the cells and act as an epigenetic inheritor response to target pathogens through RNAs. COIVID-19 resistance activated plasma-derived exosomes are either responsible for the effects of plasma beyond the contained immune antibodies or could be inhibitory. The proposed hypothesis suggests that preselecting the plasma-derived antibodies and RNAs merged exosomes would be an optimized therapeutic tactic for COVID-19 patients. We suggest that, the CPExo has a multi-potential effect for treatment efficacy by acting as immunotherapeutic, drug carrier, and diagnostic target with noncoding genetic materials as a biomarker.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Exosomes/immunology , Plasma/immunology , Adaptive Immunity/immunology , Antibodies/immunology , Antigens/immunology , DNA/immunology , Humans , Immunization, Passive , RNA/immunology , SARS-CoV-2/immunology
7.
Sci Rep ; 11(1): 13638, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1294482

ABSTRACT

Human cells respond to infection by SARS-CoV-2, the virus that causes COVID-19, by producing cytokines including type I and III interferons (IFNs) and proinflammatory factors such as IL6 and TNF. IFNs can limit SARS-CoV-2 replication but cytokine imbalance contributes to severe COVID-19. We studied how cells detect SARS-CoV-2 infection. We report that the cytosolic RNA sensor MDA5 was required for type I and III IFN induction in the lung cancer cell line Calu-3 upon SARS-CoV-2 infection. Type I and III IFN induction further required MAVS and IRF3. In contrast, induction of IL6 and TNF was independent of the MDA5-MAVS-IRF3 axis in this setting. We further found that SARS-CoV-2 infection inhibited the ability of cells to respond to IFNs. In sum, we identified MDA5 as a cellular sensor for SARS-CoV-2 infection that induced type I and III IFNs.


Subject(s)
COVID-19/immunology , Interferon Type I/immunology , Interferon-Induced Helicase, IFIH1/immunology , Interferons/immunology , SARS-CoV-2/immunology , Cell Line , Humans , Immunity, Innate , RNA/immunology
8.
Aging (Albany NY) ; 13(5): 6273-6288, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1154950

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with a poor prognosis. The current coronavirus disease 2019 (COVID-19) shares some similarities with IPF. SARS-CoV-2 related genes have been reported to be broadly regulated by N6-methyladenosine (m6A) RNA modification. Here, we identified the association between m6A methylation regulators, COVID-19 infection pathways, and immune responses in IPF. The characteristic gene expression networks and immune infiltration patterns of m6A-SARS-CoV-2 related genes in different tissues of IPF were revealed. We subsequently evaluated the influence of these related gene expression patterns and immune infiltration patterns on the prognosis/lung function of IPF patients. The IPF cohort was obtained from the Gene Expression Omnibus dataset. Pearson correlation analysis was performed to identify the correlations among genes or cells. The CIBERSORT algorithm was used to assess the infiltration of 22 types of immune cells. The least absolute shrinkage and selection operator (LASSO) and proportional hazards model (Cox model) were used to develop the prognosis prediction model. Our research is pivotal for further understanding of the cellular and genetic links between IPF and SARS-CoV-2 infection in the context of the COVID-19 pandemic, which may contribute to providing new ideas for prognosis assessment and treatment of both diseases.


Subject(s)
Adenosine/analogs & derivatives , COVID-19/genetics , Gene Regulatory Networks , Idiopathic Pulmonary Fibrosis/genetics , Adenosine/genetics , Adenosine/immunology , Algorithms , COVID-19/diagnosis , COVID-19/immunology , Humans , Idiopathic Pulmonary Fibrosis/diagnosis , Idiopathic Pulmonary Fibrosis/immunology , Immunity , Immunity, Cellular , Prognosis , RNA/genetics , RNA/immunology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/immunology , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
9.
Aging (Albany NY) ; 13(5): 6273-6288, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1112911

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with a poor prognosis. The current coronavirus disease 2019 (COVID-19) shares some similarities with IPF. SARS-CoV-2 related genes have been reported to be broadly regulated by N6-methyladenosine (m6A) RNA modification. Here, we identified the association between m6A methylation regulators, COVID-19 infection pathways, and immune responses in IPF. The characteristic gene expression networks and immune infiltration patterns of m6A-SARS-CoV-2 related genes in different tissues of IPF were revealed. We subsequently evaluated the influence of these related gene expression patterns and immune infiltration patterns on the prognosis/lung function of IPF patients. The IPF cohort was obtained from the Gene Expression Omnibus dataset. Pearson correlation analysis was performed to identify the correlations among genes or cells. The CIBERSORT algorithm was used to assess the infiltration of 22 types of immune cells. The least absolute shrinkage and selection operator (LASSO) and proportional hazards model (Cox model) were used to develop the prognosis prediction model. Our research is pivotal for further understanding of the cellular and genetic links between IPF and SARS-CoV-2 infection in the context of the COVID-19 pandemic, which may contribute to providing new ideas for prognosis assessment and treatment of both diseases.


Subject(s)
Adenosine/analogs & derivatives , COVID-19/genetics , Gene Regulatory Networks , Idiopathic Pulmonary Fibrosis/genetics , Adenosine/genetics , Adenosine/immunology , Algorithms , COVID-19/diagnosis , COVID-19/immunology , Humans , Idiopathic Pulmonary Fibrosis/diagnosis , Idiopathic Pulmonary Fibrosis/immunology , Immunity , Immunity, Cellular , Prognosis , RNA/genetics , RNA/immunology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/immunology , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
10.
Pediatr Ann ; 49(12): e532-e536, 2020 Dec 01.
Article in English | MEDLINE | ID: covidwho-963769

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the identified cause of coronavirus disease 2019 (COVID-19), continues unabated. This fact, coupled with recurrence of COVID-19 in areas where it had been controlled, highlights the critical need for a safe and effective vaccine to prevent and mitigate this novel virus. The spike protein of SARS-CoV-2 is important in its lifecycle as well as in the development of immunity after human infection. This has prompted the selection of this antigen as a focus in developing COVID-19 vaccines. This article provides (1) a summary of the host immune responses to SARS-CoV-2 infection, (2) the vaccine platforms being used with COVID-19 vaccine candidates undergoing, or about to undergo, Phase III clinical trial testing, and (3) an overview of the key criteria necessary for COVID-19 vaccine efficacy and safety. In addition, the unique concept of vaccine-enhanced disease will be discussed. [Pediatr Ann. 2020;49(12):e532-e536.].


Subject(s)
COVID-19 Vaccines , SARS-CoV-2/immunology , Antibodies, Viral/analysis , Antibodies, Viral/immunology , Antibody-Dependent Enhancement , Drug Development , Humans , Public-Private Sector Partnerships , RNA/immunology , Recombinant Proteins/immunology , Respiratory Tract Diseases/chemically induced , Spike Glycoprotein, Coronavirus/immunology , Virus Replication/immunology
SELECTION OF CITATIONS
SEARCH DETAIL