scholarly journals Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling

2020 ◽  
Author(s):  
Benjamin Israelow ◽  
Eric Song ◽  
Tianyang Mao ◽  
Peiwen Lu ◽  
Amit Meir ◽  
...  
Keyword(s):  
Mouse Model ◽  
Type I Interferons ◽  
Type I ◽  
Adeno Associated Virus ◽  
Angiotensin Converting Enzyme 2 ◽  
Vaccine Trials ◽  
Global Pandemic ◽  
Depth Analysis ◽  
Rapid Deployment

AbstractSevere Acute Respiratory Syndrome-Coronavirus 2 (SARS-Cov-2) has caused over 5,000,000 cases of Coronavirus disease (COVID-19) with significant fatality rate.1–3 Due to the urgency of this global pandemic, numerous therapeutic and vaccine trials have begun without customary safety and efficacy studies.4 Laboratory mice have been the stalwart of these types of studies; however, they do not support infection by SARS-CoV-2 due to the inability of its spike (S) protein to engage the mouse ortholog of its human entry receptor angiotensin-converting enzyme 2 (hACE2). While hACE2 transgenic mice support infection and pathogenesis,5 these mice are currently limited in availability and are restricted to a single genetic background. Here we report the development of a mouse model of SARS-CoV-2 based on adeno associated virus (AAV)-mediated expression of hACE2. These mice support viral replication and antibody production and exhibit pathologic findings found in COVID-19 patients as well as non-human primate models. Moreover, we show that type I interferons are unable to control SARS-CoV2 replication and drive pathologic responses. Thus, the hACE2-AAV mouse model enables rapid deployment for in-depth analysis following robust SARS-CoV-2 infection with authentic patient-derived virus in mice of diverse genetic backgrounds. This represents a much-needed platform for rapidly testing prophylactic and therapeutic strategies to combat COVID-19.

scholarly journals Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling

2020 ◽  
Vol 217 (12) ◽  
Author(s):  
Benjamin Israelow ◽  
Eric Song ◽  
Tianyang Mao ◽  
Peiwen Lu ◽  
Amit Meir ◽  
...  
Keyword(s):  
Mouse Model ◽  
Vaccine Development ◽  
Type I Interferons ◽  
Type I ◽  
Adeno Associated Virus ◽  
Angiotensin Converting Enzyme 2 ◽  
Depth Analysis ◽  
Rapid Deployment

Severe acute respiratory syndrome–coronavirus 2 (SARS-Cov-2) has caused over 13,000,000 cases of coronavirus disease (COVID-19) with a significant fatality rate. Laboratory mice have been the stalwart of therapeutic and vaccine development; however, they do not support infection by SARS-CoV-2 due to the virus’s inability to use the mouse orthologue of its human entry receptor angiotensin-converting enzyme 2 (hACE2). While hACE2 transgenic mice support infection and pathogenesis, these mice are currently limited in availability and are restricted to a single genetic background. Here we report the development of a mouse model of SARS-CoV-2 based on adeno-associated virus (AAV)–mediated expression of hACE2. These mice support viral replication and exhibit pathological findings found in COVID-19 patients. Moreover, we show that type I interferons do not control SARS-CoV-2 replication in vivo but are significant drivers of pathological responses. Thus, the AAV-hACE2 mouse model enables rapid deployment for in-depth analysis following robust SARS-CoV-2 infection with authentic patient-derived virus in mice of diverse genetic backgrounds.

The Role of Toll-Like Receptors and Type I Interferons in Host Responses to Bacteria

2009 ◽  
Vol 5 (2) ◽  
pp. 143-149
Author(s):  
Marja Ojaniemi ◽  
Mari Liljeroos ◽  
Reetta Vuolteenaho
Keyword(s):  
Type I Interferons ◽  
Host Responses ◽  
Type I ◽  
Toll Like Receptors

scholarly journals Bacterial Cyclic Dinucleotides and the cGAS–cGAMP–STING Pathway: A Role in Periodontitis?

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 675
Author(s):  
Samira Elmanfi ◽  
Mustafa Yilmaz ◽  
Wilson W. S. Ong ◽  
Kofi S. Yeboah ◽  
Herman O. Sintim ◽  
...  
Keyword(s):  
Immune Response ◽  
Periodontal Disease ◽  
Innate Immune ◽  
Host Cells ◽  
Type I Interferons ◽  
Type I ◽  
Vaccine Adjuvants ◽  
Cyclic Dinucleotides ◽  
Sting Pathway

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides—including c-di-GMP, c-di-AMP, and cGAMP—of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms “STING”, “TBK 1”, “IRF3”, and “cGAS”—alone, or together with “periodontitis”. Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology.

scholarly journals A protective role of IRF3 and IRF7 signalling downstream TLRs in the development of vein graft disease via type I interferons

2017 ◽  
Vol 282 (6) ◽  
pp. 522-536 ◽  
Author(s):  
K. H. Simons ◽  
H. A. B. Peters ◽  
J. W. Jukema ◽  
M. R. de Vries ◽  
P. H. A. Quax
Keyword(s):  
Vein Graft ◽  
Protective Role ◽  
Type I Interferons ◽  
Type I ◽  
Vein Graft Disease ◽  
Graft Disease

scholarly journals THE ROLE OF TYPE-I INTERFERONS IN POLY I:C INDUCED SICKNESS BEHAVIOUR

2014 ◽  
Vol 8 ◽  
Author(s):  
Murray Carol ◽  
O Loughlin Elaine ◽  
Cunningham Colm
Keyword(s):  
Type I Interferons ◽  
Poly I:C ◽  
Type I ◽  
Sickness Behaviour

The protective role of Toll-like receptor 3 and type-I interferons in the pathophysiology of vein graft disease

2018 ◽  
Vol 121 ◽  
pp. 16-24 ◽  
Author(s):  
K.H. Simons ◽  
M.R. de Vries ◽  
H.A.B. Peters ◽  
J.F. Hamming ◽  
J.W. Jukema ◽  
...  
Keyword(s):  
Vein Graft ◽  
Protective Role ◽  
Type I Interferons ◽  
Type I ◽  
Toll Like Receptor ◽  
Vein Graft Disease ◽  
Graft Disease

Multiple effects of immunostimulatory DNA on T cells and the role of type I interferons

2001 ◽  
pp. 77-84 ◽  
Author(s):  
Siquan Sun ◽  
Xiaohong Zhang ◽  
David Tough ◽  
Jonathan Sprent
Keyword(s):  
T Cells ◽  
Type I Interferons ◽  
Type I ◽  
Immunostimulatory Dna

An Updated Review on the Role of Single Nucleotide Polymorphisms in COVID-19 Disease Severity: A Global Aspect

2022 ◽  
Vol 23 ◽  
Author(s):  
Jun Wei Ng ◽  
Eric Tzyy Jiann Chong ◽  
Ping-Chin Lee
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Pandemic ◽  
Global Aspect ◽  
Common Risk Factors ◽  
Severity Of The Disease ◽  
Ace2 Gene

Abstract: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and recently has become a serious global pandemic. Age, gender, and comorbidities are known to be common risk factors for severe COVID-19 but are not enough to fully explain the magnitude of their effect on the risk of severity of the disease. Single nucleotide polymorphisms (SNPs) in several genes have been reported as a genetic factor contributing to COVID-19 severity. This comprehensive review focuses on the association between SNPs in four important genes and COVID-19 severity in a global aspect. We discuss a total of 39 SNPs in this review: five SNPs in the ABO gene, nine SNPs in the angiotensin-converting enzyme 2 (ACE2) gene, 19 SNPs in the transmembrane protease serine 2 (TMPRSS2) gene, and six SNPs in the toll-like receptor 7 (TLR7) gene. These SNPs data could assist in monitoring an individual's risk of severe COVID-19 disease, and therefore personalized management and pharmaceutical treatment could be planned in COVID-19 patients.

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