Arinjay Banerjee, Patrick Budylowski, Daniel Richard, Hassaan Maan, Jennifer A. Aguiar, Nader El-Sayes, Michael R. D’Agostino, Benjamin J.-M. Tremblay, Sam Afkhami, Mehran Karimzadeh, Lily Yip, Mario Ostrowski, Jeremy A. Hirota, Robert Kozak, Terence D. Capellini, Matthew S. Miller, Andrew G. McArthur, Bo Wang, Andrew C. Doxey, Samira Mubareka, & Karen Mossman
bioRxiv doi:10.1101/2020.06.18.158154
Two highly pathogenic human coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have evolved proteins that can inhibit host antiviral responses, likely contributing to disease progression and high case-fatality rates. SARS-CoV-2 emerged in December 2019 resulting in a global pandemic. Recent studies have shown that SARS-CoV-2 is unable to induce a robust type I interferon (IFN) response in human cells, leading to speculation about the ability of SARS-CoV-2 to inhibit innate antiviral responses. However, innate antiviral responses are dynamic in nature and gene expression levels rapidly change within minutes to hours. In this study, we have performed a time series RNA-seq and selective immunoblot analysis of SARS-CoV-2 infected lung (Calu-3) cells to characterize early virus-host processes. SARS-CoV-2 infection upregulated transcripts for type I IFNs and interferon stimulated genes (ISGs) after 12 hours. Furthermore, we analyzed the ability of SARS-CoV-2 to inhibit type I IFN production and downstream antiviral signaling in human cells. Using exogenous stimuli, we discovered that SARS-CoV-2 is unable to modulate IFNβ production and downstream expression of ISGs, such as IRF7 and IFIT1. Thus, data from our study indicate that SARS-CoV-2 may have evolved additional mechanisms, such as masking of viral nucleic acid sensing by host cells to mount a dampened innate antiviral response. Further studies are required to fully identify the range of immune-modulatory strategies of SARS-CoV-2.
Maan, H., H. Mbareche, A.R. Raphenya, A. Banerjee, J.A. Nasir, R.A. Kozak, N. Knox, S. Mubareka, A.G. McArthur, & B. Wang.
The Lancet Digital Health, in press.
The ongoing COVID-19 pandemic is the greatest health-care challenge of this generation. Early viral genome sequencing studies of small cohorts have indicated the possibility of distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genotypes.1 If these subtypes result in an altered virus tropism or pathogenesis in infected hosts, this could have immediate implications for vaccine design, drug development, and efforts to control the pandemic. Therefore, the genomic surveillance and characterisation of circulating viral strains is a high priority for research and development. To facilitate the epidemiological tracking of SARS-CoV-2, researchers worldwide have created various web-portals and tools, such as the Johns Hopkins University COVID-19 dashboard. An unprecedented effort to make COVID-19-related data accessible in near real-time has resulted in more than 25 000 publicly available genome sequences of SARS-CoV-2 on Global Initiative on Sharing All Influenza Data (GISAID). Although platforms to survey epidemiological data are prevalent, tools that summarise publicly available viral genome data are scarce and those that are available do not offer users the ability to analyse in-house sequencing data. To address this gap, we have developed an accessible application, the COVID-19 Genotyping Tool (CGT).
Full paper at The Lancet Digital Health.
Featured on CBC’s The National: Scientists develop an app that tracks how COVID-19 mutates person-to-person
Thanks to hard work by Jalees Nasir, Amos Raphenya, Dr. Kendrick Smith (Perimeter Institute), and Dr. Finlay Maguire (Dalhousie) with help from our Ontario Coronavirus Genomics Coalition (ONCoV) colleagues, particularly Dr. Jared Simpson (OICR), Dr. Hamza Mbareche (Sunnybrook Health Sciences Centre), Dr. Hassaan Mann (Vector Institute), and Dr. Natalie Knox (Public Health Agency of Canada), the McArthur lab is proud to release the SARS-CoV-2 Illumina GeNome Assembly Line (SIGNAL) bioinformatics workflow for SARS-CoV-2 genome analysis based on Illumina sequencing data, available here: https://github.com/jaleezyy/covid-19-signal
The McArthur lab welcomes Ahmed Draia for an internship placement as part of McMaster’s Masters of Biomedical Discovery & Commercialization (MBDC) program. Reflective of his joint training in business and biomedical discovery, Ahmed will be spending 4 months with us as Project Manager for our Ontario Coronavirus Genomics Coalition (ONCoV) work.
The McArthur lab is honoured to collaborate with our clinical colleagues across Ontario in sequencing of SARS-CoV-2 clinical isolates, to better understand the epidemiology of the pandemic. Our colleague Dr. Samira Mubareka explains it best:
Dr. Samira Mubareka
Infectious Diseases Physician & Virologist – Sunnybrook Health Sciences Centre & Research Institute and the University of Toronto
Banerjee, A., J.A. Nasir, P. Budylowski, L. Yip, P. Aftanas, N. Christie, A. Ghalami, K. Baid, A.R. Raphenya, J.A. Hirota, M.S. Miller, A.J. McGeer, M.A. Ostrowski, R.A. Kozak, A.G. McArthur, K. Mossman, & S. Mubareka
bioRxiv doi:10.1101/2020.04.11.037382
SARS-CoV-2 emerged in December 2019 in Wuhan, China and has since infected over 1.5 million people, of which over 100,000 have died. As SARS-CoV-2 spreads across the planet, speculations remain about the evolution of the virus and the range of human cells that can be infected by SARS-CoV-2. In this study, we report the isolation of SARS-CoV-2 from two COVID-19 patients in Toronto, Canada. We determined the genomic sequences of the two isolates and identified single nucleotide changes in representative populations of our virus stocks. More importantly, we have tested a wide range of human immune cells for infectivity with SARS-CoV-2. We confirm from our studies that human primary peripheral blood mononuclear cells (PBMCs) are not permissive to SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor any small nucleotide polymorphisms in the virus and to continue to isolate circulating strains of the virus to determine cell susceptibility and pathogenicity using in vitro and in vivo infection models.
Hear Arinjay & Andrew talk about their SARS-CoV-2 work: https://www.youtube.com/watch?v=SVzDHESnssg
See also: McMaster researcher plays key role in isolating COVID-19 virus for use in urgent research
Quick update on the status of the McArthur Lab and the Comprehensive Antibiotic Resistance Database. While our home institution McMaster University is closed to on-site research and undergraduate/graduate teaching, all McArthur Lab members and CARD staff are working from home. However, like many genomics labs in Canada we are directly helping our clinical colleagues in analysis of SARS-CoV-2 sequences, lending processing power, staff time, and expertise. Response time for CARD might be a bit slow as we are stretched a bit thin. But on May 1st, 2020 we will be joined by William Huynh as Junior CARD Curator & Help Desk manager. We are excited to have William join us and expect to come back strong supporting the AMR research community in May.