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The emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more recently, the independent evolution of multiple SARS-CoV-2 variants has generated renewed interest in virus evolution and cross-species transmission. While all known human coronaviruses (HCoVs) are speculated to have originated in animals, very little is known about their evolutionary history and factors that enable some CoVs to co-exist with humans as low pathogenic and endemic infections (HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1), while others, such as SARS-CoV, MERS-CoV and SARS-CoV-2 have evolved to cause severe disease. In this review, we highlight the origins of all known HCoVs and map positively selected for mutations within HCoV proteins to discuss the evolutionary trajectory of SARS-CoV-2. Furthermore, we discuss emerging mutations within SARS-CoV-2 and variants of concern (VOC), along with highlighting the demonstrated or speculated impact of these mutations on virus transmission, pathogenicity, and neutralization by natural or vaccine-mediated immunity.
Jalen Singh; Pranav Pandit; Andrew G. McArthur; Arinjay Banerjee; Karen Mossman. Evolutionary trajectory of SARS-CoV-2 and emerging variants. Virology Journal 2021, 18, 1 -21.
AMA StyleJalen Singh, Pranav Pandit, Andrew G. McArthur, Arinjay Banerjee, Karen Mossman. Evolutionary trajectory of SARS-CoV-2 and emerging variants. Virology Journal. 2021; 18 (1):1-21.
Chicago/Turabian StyleJalen Singh; Pranav Pandit; Andrew G. McArthur; Arinjay Banerjee; Karen Mossman. 2021. "Evolutionary trajectory of SARS-CoV-2 and emerging variants." Virology Journal 18, no. 1: 1-21.
The likely animal source of SARS-CoV-2 remains speculative. A recent study published in Cell by Zhou et al. reported the detection of novel alpha- and betacoronaviruses, including SARS-CoV-2-related viruses in bats.
Arinjay Banerjee. Virus hunters: Discovering the evolutionary origins of SARS-CoV-2. Cell Host & Microbe 2021, 29, 1031 -1033.
AMA StyleArinjay Banerjee. Virus hunters: Discovering the evolutionary origins of SARS-CoV-2. Cell Host & Microbe. 2021; 29 (7):1031-1033.
Chicago/Turabian StyleArinjay Banerjee. 2021. "Virus hunters: Discovering the evolutionary origins of SARS-CoV-2." Cell Host & Microbe 29, no. 7: 1031-1033.
Summary Type I interferons (IFNs) are our first line of defense against virus infection. Recent studies have suggested the ability of SARS-CoV-2 proteins to inhibit IFN responses. Emerging data also suggest that timing and extent of IFN production is associated with manifestation of COVID-19 severity. In spite of progress in understanding how SARS-CoV-2 activates antiviral responses, mechanistic studies into wild-type SARS-CoV-2-mediated induction and inhibition of human type I IFN responses are scarce. Here we demonstrate that SARS-CoV-2 infection induces a type I IFN response in vitro and in moderate cases of COVID-19. In vitro stimulation of type I IFN expression and signaling in human airway epithelial cells is associated with activation of canonical transcriptions factors, and SARS-CoV-2 is unable to inhibit exogenous induction of these responses. Furthermore, we show that physiological levels of IFNα detected in patients with moderate COVID-19 is sufficient to suppress SARS-CoV-2 replication in human airway cells.
Arinjay Banerjee; Nader El-Sayes; Patrick Budylowski; Rajesh Abraham Jacob; Daniel Richard; Hassaan Maan; Jennifer A. Aguiar; Wael L. Demian; Kaushal Baid; Michael R. D'Agostino; Jann Catherine Ang; Tetyana Murdza; Benjamin J.-M. Tremblay; Sam Afkhami; Mehran Karimzadeh; Aaron T. Irving; Lily Yip; Mario Ostrowski; Jeremy A. Hirota; Robert Kozak; Terence D. Capellini; Matthew S. Miller; Bo Wang; Samira Mubareka; Allison J. McGeer; Andrew G. McArthur; Andrew C. Doxey; Karen Mossman. Experimental and natural evidence of SARS-CoV-2-infection-induced activation of type I interferon responses. iScience 2021, 102477 .
AMA StyleArinjay Banerjee, Nader El-Sayes, Patrick Budylowski, Rajesh Abraham Jacob, Daniel Richard, Hassaan Maan, Jennifer A. Aguiar, Wael L. Demian, Kaushal Baid, Michael R. D'Agostino, Jann Catherine Ang, Tetyana Murdza, Benjamin J.-M. Tremblay, Sam Afkhami, Mehran Karimzadeh, Aaron T. Irving, Lily Yip, Mario Ostrowski, Jeremy A. Hirota, Robert Kozak, Terence D. Capellini, Matthew S. Miller, Bo Wang, Samira Mubareka, Allison J. McGeer, Andrew G. McArthur, Andrew C. Doxey, Karen Mossman. Experimental and natural evidence of SARS-CoV-2-infection-induced activation of type I interferon responses. iScience. 2021; ():102477.
Chicago/Turabian StyleArinjay Banerjee; Nader El-Sayes; Patrick Budylowski; Rajesh Abraham Jacob; Daniel Richard; Hassaan Maan; Jennifer A. Aguiar; Wael L. Demian; Kaushal Baid; Michael R. D'Agostino; Jann Catherine Ang; Tetyana Murdza; Benjamin J.-M. Tremblay; Sam Afkhami; Mehran Karimzadeh; Aaron T. Irving; Lily Yip; Mario Ostrowski; Jeremy A. Hirota; Robert Kozak; Terence D. Capellini; Matthew S. Miller; Bo Wang; Samira Mubareka; Allison J. McGeer; Andrew G. McArthur; Andrew C. Doxey; Karen Mossman. 2021. "Experimental and natural evidence of SARS-CoV-2-infection-induced activation of type I interferon responses." iScience , no. : 102477.
The origin and zoonotic transmission route of SARS-CoV-2 remain speculative. We discuss scenarios for the zoonotic emergence of SARS-CoV-2, and also explore the missing evidence and ecological considerations that are necessary to confidently identify the origin and transmission route of SARS-CoV-2 and to prevent future pandemics of zoonotic viruses.
Arinjay Banerjee; Andrew C. Doxey; Karen Mossman; Aaron T. Irving. Unraveling the Zoonotic Origin and Transmission of SARS-CoV-2. Trends in Ecology & Evolution 2020, 36, 180 -184.
AMA StyleArinjay Banerjee, Andrew C. Doxey, Karen Mossman, Aaron T. Irving. Unraveling the Zoonotic Origin and Transmission of SARS-CoV-2. Trends in Ecology & Evolution. 2020; 36 (3):180-184.
Chicago/Turabian StyleArinjay Banerjee; Andrew C. Doxey; Karen Mossman; Aaron T. Irving. 2020. "Unraveling the Zoonotic Origin and Transmission of SARS-CoV-2." Trends in Ecology & Evolution 36, no. 3: 180-184.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged to cause widespread infections in humans. SARS-CoV-2 infections have been reported in the Kingdom of Saudi Arabia, where Middle East respiratory syndrome coronavirus (MERS-CoV) causes seasonal outbreaks with a case fatality rate of ~37 %. Here we show that there exists a theoretical possibility of future recombination events between SARS-CoV-2 and MERS-CoV RNA. Through computational analyses, we have identified homologous genomic regions within the ORF1ab and S genes that could facilitate recombination, and have analysed co-expression patterns of the cellular receptors for SARS-CoV-2 and MERS-CoV, ACE2 and DPP4, respectively, to identify human anatomical sites that could facilitate co-infection. Furthermore, we have investigated the likely susceptibility of various animal species to MERS-CoV and SARS-CoV-2 infection by comparing known virus spike protein–receptor interacting residues. In conclusion, we suggest that a recombination between SARS-CoV-2 and MERS-CoV RNA is possible and urge public health laboratories in high-risk areas to develop diagnostic capability for the detection of recombined coronaviruses in patient samples.
Arinjay Banerjee; Andrew C. Doxey; Benjamin J.-M. Tremblay; Michael Mansfield; Sonu Subudhi; Jeremy A. Hirota; Matthew S. Miller; Andrew G. McArthur; Samira Mubareka; Karen Mossman. Predicting the recombination potential of severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus. Journal of General Virology 2020, 101, 1251 -1260.
AMA StyleArinjay Banerjee, Andrew C. Doxey, Benjamin J.-M. Tremblay, Michael Mansfield, Sonu Subudhi, Jeremy A. Hirota, Matthew S. Miller, Andrew G. McArthur, Samira Mubareka, Karen Mossman. Predicting the recombination potential of severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus. Journal of General Virology. 2020; 101 (12):1251-1260.
Chicago/Turabian StyleArinjay Banerjee; Andrew C. Doxey; Benjamin J.-M. Tremblay; Michael Mansfield; Sonu Subudhi; Jeremy A. Hirota; Matthew S. Miller; Andrew G. McArthur; Samira Mubareka; Karen Mossman. 2020. "Predicting the recombination potential of severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus." Journal of General Virology 101, no. 12: 1251-1260.
Since its emergence in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected ≈6 million persons worldwide. As SARS-CoV-2 spreads across the planet, we explored the range of human cells that can be infected by this virus. We isolated SARS-CoV-2 from 2 infected patients in Toronto, Canada; determined the genomic sequences; and identified single-nucleotide changes in representative populations of our virus stocks. We also tested a wide range of human immune cells for productive infection with SARS-CoV-2. We confirm that human primary peripheral blood mononuclear cells are not permissive for SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor single-nucleotide polymorphisms in the virus and to continue to isolate circulating viruses to determine viral genotype and phenotype by using in vitro and in vivo infection models.
Arinjay Banerjee; Jalees Nasir; Patrick Budylowski; Lily Yip; Patryk Aftanas; Natasha Christie; Ayoob Ghalami; Kaushal Baid; Amogelang R. Raphenya; Jeremy A. Hirota; Matthew S. Miller; Allison J. McGeer; Mario Ostrowski; Robert A. Kozak; Andrew G. McArthur; Karen Mossman; Samira Mubareka. Isolation, Sequence, Infectivity, and Replication Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2. Emerging Infectious Diseases 2020, 26, 2054 -2063.
AMA StyleArinjay Banerjee, Jalees Nasir, Patrick Budylowski, Lily Yip, Patryk Aftanas, Natasha Christie, Ayoob Ghalami, Kaushal Baid, Amogelang R. Raphenya, Jeremy A. Hirota, Matthew S. Miller, Allison J. McGeer, Mario Ostrowski, Robert A. Kozak, Andrew G. McArthur, Karen Mossman, Samira Mubareka. Isolation, Sequence, Infectivity, and Replication Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2. Emerging Infectious Diseases. 2020; 26 (9):2054-2063.
Chicago/Turabian StyleArinjay Banerjee; Jalees Nasir; Patrick Budylowski; Lily Yip; Patryk Aftanas; Natasha Christie; Ayoob Ghalami; Kaushal Baid; Amogelang R. Raphenya; Jeremy A. Hirota; Matthew S. Miller; Allison J. McGeer; Mario Ostrowski; Robert A. Kozak; Andrew G. McArthur; Karen Mossman; Samira Mubareka. 2020. "Isolation, Sequence, Infectivity, and Replication Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2." Emerging Infectious Diseases 26, no. 9: 2054-2063.
Genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is increasingly important to monitor the transmission and adaptive evolution of the virus. The accessibility of high-throughput methods and polymerase chain reaction (PCR) has facilitated a growing ecosystem of protocols. Two differing protocols are tiling multiplex PCR and bait capture enrichment. Each method has advantages and disadvantages but a direct comparison with different viral RNA concentrations has not been performed to assess the performance of these approaches. Here we compare Liverpool amplification, ARTIC amplification, and bait capture using clinical diagnostics samples. All libraries were sequenced using an Illumina MiniSeq with data analyzed using a standardized bioinformatics workflow (SARS-CoV-2 Illumina GeNome Assembly Line; SIGNAL). One sample showed poor SARS-CoV-2 genome coverage and consensus, reflective of low viral RNA concentration. In contrast, the second sample had a higher viral RNA concentration, which yielded good genome coverage and consensus. ARTIC amplification showed the highest depth of coverage results for both samples, suggesting this protocol is effective for low concentrations. Liverpool amplification provided a more even read coverage of the SARS-CoV-2 genome, but at a lower depth of coverage. Bait capture enrichment of SARS-CoV-2 cDNA provided results on par with amplification. While only two clinical samples were examined in this comparative analysis, both the Liverpool and ARTIC amplification methods showed differing efficacy for high and low concentration samples. In addition, amplification-free bait capture enriched sequencing of cDNA is a viable method for generating a SARS-CoV-2 genome sequence and for identification of amplification artifacts.
Jalees A. Nasir; Robert A. Kozak; Patryk Aftanas; Amogelang R. Raphenya; Kendrick M. Smith; Finlay Maguire; Hassaan Maan; Muhannad Alruwaili; Arinjay Banerjee; Hamza Mbareche; Brian P. Alcock; Natalie C. Knox; Karen Mossman; Bo Wang; Julian A. Hiscox; Andrew G. McArthur; Samira Mubareka. A Comparison of Whole Genome Sequencing of SARS-CoV-2 Using Amplicon-Based Sequencing, Random Hexamers, and Bait Capture. Viruses 2020, 12, 895 .
AMA StyleJalees A. Nasir, Robert A. Kozak, Patryk Aftanas, Amogelang R. Raphenya, Kendrick M. Smith, Finlay Maguire, Hassaan Maan, Muhannad Alruwaili, Arinjay Banerjee, Hamza Mbareche, Brian P. Alcock, Natalie C. Knox, Karen Mossman, Bo Wang, Julian A. Hiscox, Andrew G. McArthur, Samira Mubareka. A Comparison of Whole Genome Sequencing of SARS-CoV-2 Using Amplicon-Based Sequencing, Random Hexamers, and Bait Capture. Viruses. 2020; 12 (8):895.
Chicago/Turabian StyleJalees A. Nasir; Robert A. Kozak; Patryk Aftanas; Amogelang R. Raphenya; Kendrick M. Smith; Finlay Maguire; Hassaan Maan; Muhannad Alruwaili; Arinjay Banerjee; Hamza Mbareche; Brian P. Alcock; Natalie C. Knox; Karen Mossman; Bo Wang; Julian A. Hiscox; Andrew G. McArthur; Samira Mubareka. 2020. "A Comparison of Whole Genome Sequencing of SARS-CoV-2 Using Amplicon-Based Sequencing, Random Hexamers, and Bait Capture." Viruses 12, no. 8: 895.
In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilises angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) host molecules for viral entry. ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection. Additional host molecules including ADAM17, cathepsin L, CD147 and GRP78 may also function as receptors for SARS-CoV-2. To determine the expression and in situ localisation of candidate SARS-CoV-2 receptors in the respiratory mucosa, we analysed gene expression datasets from airway epithelial cells of 515 healthy subjects, gene promoter activity analysis using the FANTOM5 dataset containing 120 distinct sample types, single cell RNA sequencing (scRNAseq) of 10 healthy subjects, proteomic datasets, immunoblots on multiple airway epithelial cell types, and immunohistochemistry on 98 human lung samples. We demonstrate absent to low ACE2 promoter activity in a variety of lung epithelial cell samples and low ACE2 gene expression in both microarray and scRNAseq datasets of epithelial cell populations. Consistent with gene expression, rare ACE2 protein expression was observed in the airway epithelium and alveoli of human lung, confirmed with proteomics. We present confirmatory evidence for the presence of TMPRSS2, CD147 and GRP78 protein in vitro in airway epithelial cells and confirm broad in situ protein expression of CD147 and GRP78 in the respiratory mucosa. Collectively, our data suggest the presence of a mechanism dynamically regulating ACE2 expression in human lung, perhaps in periods of SARS-CoV-2 infection, and also suggest that alternative receptors for SARS-CoV-2 exist to facilitate initial host cell infection.
Jennifer A. Aguiar; Benjamin J-M. Tremblay; Michael J. Mansfield; Owen Woody; Briallen Lobb; Arinjay Banerjee; Abiram Chandiramohan; Nicholas Tiessen; Quynh Cao; Anna Dvorkin-Gheva; Spencer Revill; Matthew S. Miller; Christopher Carlsten; Louise Organ; Chitra Joseph; Alison John; Paul Hanson; Richard C. Austin; Bruce M. McManus; Gisli Jenkins; Karen Mossman; Kjetil Ask; Andrew C. Doxey; Jeremy A. Hirota. Gene expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue. European Respiratory Journal 2020, 56, 2001123 .
AMA StyleJennifer A. Aguiar, Benjamin J-M. Tremblay, Michael J. Mansfield, Owen Woody, Briallen Lobb, Arinjay Banerjee, Abiram Chandiramohan, Nicholas Tiessen, Quynh Cao, Anna Dvorkin-Gheva, Spencer Revill, Matthew S. Miller, Christopher Carlsten, Louise Organ, Chitra Joseph, Alison John, Paul Hanson, Richard C. Austin, Bruce M. McManus, Gisli Jenkins, Karen Mossman, Kjetil Ask, Andrew C. Doxey, Jeremy A. Hirota. Gene expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue. European Respiratory Journal. 2020; 56 (3):2001123.
Chicago/Turabian StyleJennifer A. Aguiar; Benjamin J-M. Tremblay; Michael J. Mansfield; Owen Woody; Briallen Lobb; Arinjay Banerjee; Abiram Chandiramohan; Nicholas Tiessen; Quynh Cao; Anna Dvorkin-Gheva; Spencer Revill; Matthew S. Miller; Christopher Carlsten; Louise Organ; Chitra Joseph; Alison John; Paul Hanson; Richard C. Austin; Bruce M. McManus; Gisli Jenkins; Karen Mossman; Kjetil Ask; Andrew C. Doxey; Jeremy A. Hirota. 2020. "Gene expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue." European Respiratory Journal 56, no. 3: 2001123.
Hassaan Maan; Hamza Mbareche; Amogelang R Raphenya; Arinjay Banerjee; Jalees A Nasir; Robert A Kozak; Natalie Knox; Samira Mubareka; Andrew G McArthur; Bo Wang. Genotyping SARS-CoV-2 through an interactive web application. The Lancet Digital Health 2020, 2, e340 -e341.
AMA StyleHassaan Maan, Hamza Mbareche, Amogelang R Raphenya, Arinjay Banerjee, Jalees A Nasir, Robert A Kozak, Natalie Knox, Samira Mubareka, Andrew G McArthur, Bo Wang. Genotyping SARS-CoV-2 through an interactive web application. The Lancet Digital Health. 2020; 2 (7):e340-e341.
Chicago/Turabian StyleHassaan Maan; Hamza Mbareche; Amogelang R Raphenya; Arinjay Banerjee; Jalees A Nasir; Robert A Kozak; Natalie Knox; Samira Mubareka; Andrew G McArthur; Bo Wang. 2020. "Genotyping SARS-CoV-2 through an interactive web application." The Lancet Digital Health 2, no. 7: e340-e341.
SUMMARY Type I interferons (IFNs) are our first line of defence against a virus. Protein over-expression studies have suggested the ability of SARS-CoV-2 proteins to block IFN responses. Emerging data also suggest that timing and extent of IFN production is associated with manifestation of COVID-19 severity. In spite of progress in understanding how SARS-CoV-2 activates antiviral responses, mechanistic studies into wildtype SARS-CoV-2-mediated induction and inhibition of human type I IFN responses are lacking. Here we demonstrate that SARS-CoV-2 infection induces a mild type I IFN response in vitro and in moderate cases of COVID-19. In vitro stimulation of type I IFN expression and signaling in human airway epithelial cells is associated with activation of canonical transcriptions factors, and SARS-CoV-2 is unable to inhibit exogenous induction of these responses. Our data demonstrate that SARS-CoV-2 is not adept in blocking type I IFN responses and provide support for ongoing IFN clinical trials.
Arinjay Banerjee; Nader El-Sayes; Patrick Budylowski; Daniel Richard; Hassaan Maan; Jennifer A. Aguiar; Kaushal Baid; Michael R. D’Agostino; Jann Catherine Ang; Benjamin J.-M. Tremblay; Sam Afkhami; Mehran Karimzadeh; Aaron T. Irving; Lily Yip; Mario A Ostrowski; Jeremy A. Hirota; Robert Kozak; Terence D. Capellini; Matthew S. Miller; Bo Wang; Samira Mubareka; Allison J. McGeer; Andrew G. McArthur; Andrew C. Doxey; Karen Mossman. Experimental and natural evidence of SARS-CoV-2 infection-induced activation of type I interferon responses. 2020, 1 .
AMA StyleArinjay Banerjee, Nader El-Sayes, Patrick Budylowski, Daniel Richard, Hassaan Maan, Jennifer A. Aguiar, Kaushal Baid, Michael R. D’Agostino, Jann Catherine Ang, Benjamin J.-M. Tremblay, Sam Afkhami, Mehran Karimzadeh, Aaron T. Irving, Lily Yip, Mario A Ostrowski, Jeremy A. Hirota, Robert Kozak, Terence D. Capellini, Matthew S. Miller, Bo Wang, Samira Mubareka, Allison J. McGeer, Andrew G. McArthur, Andrew C. Doxey, Karen Mossman. Experimental and natural evidence of SARS-CoV-2 infection-induced activation of type I interferon responses. . 2020; ():1.
Chicago/Turabian StyleArinjay Banerjee; Nader El-Sayes; Patrick Budylowski; Daniel Richard; Hassaan Maan; Jennifer A. Aguiar; Kaushal Baid; Michael R. D’Agostino; Jann Catherine Ang; Benjamin J.-M. Tremblay; Sam Afkhami; Mehran Karimzadeh; Aaron T. Irving; Lily Yip; Mario A Ostrowski; Jeremy A. Hirota; Robert Kozak; Terence D. Capellini; Matthew S. Miller; Bo Wang; Samira Mubareka; Allison J. McGeer; Andrew G. McArthur; Andrew C. Doxey; Karen Mossman. 2020. "Experimental and natural evidence of SARS-CoV-2 infection-induced activation of type I interferon responses." , no. : 1.
MHC class II (MHCII) has recently been identified as a cellular receptor for bat influenza viruses. Here, we discuss the possible implications of viral exploitation of this critical host defense molecule and highlight the need for more intense study of bat–influenza virus interactions.
Arinjay Banerjee; Karen L. Mossman; Matthew S. Miller. Bat Influenza Viruses: Making a Double Agent of MHC Class II. Trends in Microbiology 2020, 28, 703 -706.
AMA StyleArinjay Banerjee, Karen L. Mossman, Matthew S. Miller. Bat Influenza Viruses: Making a Double Agent of MHC Class II. Trends in Microbiology. 2020; 28 (9):703-706.
Chicago/Turabian StyleArinjay Banerjee; Karen L. Mossman; Matthew S. Miller. 2020. "Bat Influenza Viruses: Making a Double Agent of MHC Class II." Trends in Microbiology 28, no. 9: 703-706.
Coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are speculated to have originated in bats. The mechanisms by which these viruses are maintained in individuals or populations of reservoir bats remain an enigma. Mathematical models have predicted long-term persistent infection with low levels of periodic shedding as a likely route for virus maintenance and spillover from bats. In this study, we tested the hypothesis that bat cells and MERS coronavirus (CoV) can co-exist in vitro. To test our hypothesis, we established a long-term coronavirus infection model of bat cells that are persistently infected with MERS-CoV. We infected cells from Eptesicus fuscus with MERS-CoV and maintained them in culture for at least 126 days. We characterized the persistently infected cells by detecting virus particles, protein and transcripts. Basal levels of type I interferon in the long-term infected bat cells were higher, relative to uninfected cells, and disrupting the interferon response in persistently infected bat cells increased virus replication. By sequencing the whole genome of MERS-CoV from persistently infected bat cells, we identified that bat cells repeatedly selected for viral variants that contained mutations in the viral open reading frame 5 (ORF5) protein. Furthermore, bat cells that were persistently infected with ΔORF5 MERS-CoV were resistant to superinfection by wildtype virus, likely due to reduced levels of the virus receptor, dipeptidyl peptidase 4 (DPP4) and higher basal levels of interferon in these cells. In summary, our study provides evidence for a model of coronavirus persistence in bats, along with the establishment of a unique persistently infected cell culture model to study MERS-CoV-bat interactions.
Arinjay Banerjee; Sonu Subudhi; Noreen Rapin; Jocelyne Lew; Richa Jain; Darryl Falzarano; Vikram Misra. Selection of viral variants during persistent infection of insectivorous bat cells with Middle East respiratory syndrome coronavirus. Scientific Reports 2020, 10, 1 -15.
AMA StyleArinjay Banerjee, Sonu Subudhi, Noreen Rapin, Jocelyne Lew, Richa Jain, Darryl Falzarano, Vikram Misra. Selection of viral variants during persistent infection of insectivorous bat cells with Middle East respiratory syndrome coronavirus. Scientific Reports. 2020; 10 (1):1-15.
Chicago/Turabian StyleArinjay Banerjee; Sonu Subudhi; Noreen Rapin; Jocelyne Lew; Richa Jain; Darryl Falzarano; Vikram Misra. 2020. "Selection of viral variants during persistent infection of insectivorous bat cells with Middle East respiratory syndrome coronavirus." Scientific Reports 10, no. 1: 1-15.
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.
Arinjay Banerjee; Jalees A. Nasir; Patrick Budylowski; Lily Yip; Patryk Aftanas; Natasha Christie; Ayoob Ghalami; Kaushal Baid; Amogelang R. Raphenya; Jeremy A Hirota; Matthew S. Miller; Allison J McGeer; Mario A Ostrowski; Robert A. Kozak; Andrew G McArthur; Karen Mossman; Samira Mubareka. Isolation, sequence, infectivity and replication kinetics of SARS-CoV-2. 2020, 1 .
AMA StyleArinjay Banerjee, Jalees A. Nasir, Patrick Budylowski, Lily Yip, Patryk Aftanas, Natasha Christie, Ayoob Ghalami, Kaushal Baid, Amogelang R. Raphenya, Jeremy A Hirota, Matthew S. Miller, Allison J McGeer, Mario A Ostrowski, Robert A. Kozak, Andrew G McArthur, Karen Mossman, Samira Mubareka. Isolation, sequence, infectivity and replication kinetics of SARS-CoV-2. . 2020; ():1.
Chicago/Turabian StyleArinjay Banerjee; Jalees A. Nasir; Patrick Budylowski; Lily Yip; Patryk Aftanas; Natasha Christie; Ayoob Ghalami; Kaushal Baid; Amogelang R. Raphenya; Jeremy A Hirota; Matthew S. Miller; Allison J McGeer; Mario A Ostrowski; Robert A. Kozak; Andrew G McArthur; Karen Mossman; Samira Mubareka. 2020. "Isolation, sequence, infectivity and replication kinetics of SARS-CoV-2." , no. : 1.
The role of bats in the enzootic cycle of Lyme disease and relapsing fever-causing bacteria is a matter of speculation. In Canada, Borrelia burgdorferi sensu stricto (ss) is the genospecies that is responsible for most cases of Lyme disease in humans. In this study, we determined if big brown bats, Eptesicus fuscus, have been exposed to spirochetes from the genus Borrelia. We collected serum from 31 bats and tested them for the presence of anti-Borrelia burgdorferi antibodies using a commercial enzyme-linked immunosorbent assay (ELISA). We detected cross-reactive antibodies to Borrelia spp. in 14 of 31 bats. We confirmed the ELISA data using a commercial immunoblot assay. Pooled sera from ELISA-positive bats also cross-reacted with Borrelia antigens coated on the immunoblot strips, whereas pooled sera from ELISA-negative bats did not bind to Borrelia spp. antigens. Furthermore, to identify if bat ectoparasites, such as mites, can carry Borrelia spp., we analyzed DNA from 142 bat ectoparasites that were collected between 2003 and 2019. We detected DNA for the Borrelia burgdorferi flaB gene in one bat mite, Spinturnix americanus. The low detection rate of Borrelia burgdorferi DNA in bat ectoparasites suggests that bats are not reservoirs of this bacterium. Data from this study also raises intriguing questions about Borrelia infections in bats, including the role of humoral immunity and the ability of bats to be infected with Borrelia burgdorferi. This study can lead to more sampling efforts and controlled laboratory studies to identify if bats can be infected with Borrelia burgdorferi and the role of bat ectoparasites, such as S. americanus, in the transmission of this spirochete. Furthermore, we outlined reagents that can be used to adapt ELISA kits and immunoblot strips for use with bat sera.
Arinjay Banerjee; Kaushal Baid; Taylor Byron; Alyssa Yip; Caleb Ryan; Prasobh Raveendran Thampy; Hugh Broders; Paul Faure; Karen Mossman. Seroprevalence in Bats and Detection of Borrelia burgdorferi in Bat Ectoparasites. Microorganisms 2020, 8, 440 .
AMA StyleArinjay Banerjee, Kaushal Baid, Taylor Byron, Alyssa Yip, Caleb Ryan, Prasobh Raveendran Thampy, Hugh Broders, Paul Faure, Karen Mossman. Seroprevalence in Bats and Detection of Borrelia burgdorferi in Bat Ectoparasites. Microorganisms. 2020; 8 (3):440.
Chicago/Turabian StyleArinjay Banerjee; Kaushal Baid; Taylor Byron; Alyssa Yip; Caleb Ryan; Prasobh Raveendran Thampy; Hugh Broders; Paul Faure; Karen Mossman. 2020. "Seroprevalence in Bats and Detection of Borrelia burgdorferi in Bat Ectoparasites." Microorganisms 8, no. 3: 440.
Summary Compared with other mammals, bats harbor more zoonotic viruses per species and do not demonstrate signs of disease on infection with these viruses. To counteract infections with viruses, bats have evolved enhanced mechanisms to limit virus replication and immunopathology. However, molecular and cellular drivers of antiviral responses in bats largely remain an enigma. In this study, we demonstrate that a serine residue in IRF3 is positively selected for in multiple bat species. IRF3 is a central regulator of innate antiviral responses in mammals. Replacing the serine residue in bat IRF3 with the human leucine residue decreased antiviral protection in bat cells, whereas the addition of this serine residue in human IRF3 significantly enhanced antiviral protection in human cells. Our study provides genetic and functional evidence for enhanced IRF3-mediated antiviral responses in bats and adds support to speculations that bats have positively selected for multiple adaptations in their antiviral immune responses.
Arinjay Banerjee; Xi Zhang; Alyssa Yip; Katharina S. Schulz; Aaron Irving; Dawn Bowdish; Brian Golding; Lin-Fa Wang; Karen Mossman. Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection. iScience 2020, 23, 100958 -100958.
AMA StyleArinjay Banerjee, Xi Zhang, Alyssa Yip, Katharina S. Schulz, Aaron Irving, Dawn Bowdish, Brian Golding, Lin-Fa Wang, Karen Mossman. Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection. iScience. 2020; 23 (3):100958-100958.
Chicago/Turabian StyleArinjay Banerjee; Xi Zhang; Alyssa Yip; Katharina S. Schulz; Aaron Irving; Dawn Bowdish; Brian Golding; Lin-Fa Wang; Karen Mossman. 2020. "Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection." iScience 23, no. 3: 100958-100958.
In recent years, viruses similar to those that cause serious disease in humans and other mammals have been detected in apparently healthy bats. These include filoviruses, paramyxoviruses, and coronaviruses that cause severe diseases such as Ebola virus disease, Marburg haemorrhagic fever and severe acute respiratory syndrome (SARS) in humans. The evolution of flight in bats seem to have selected for a unique set of antiviral immune responses that control virus propagation, while limiting self-damaging inflammatory responses. Here, we summarize our current understanding of antiviral immune responses in bats and discuss their ability to co-exist with emerging viruses that cause serious disease in other mammals. We highlight how this knowledge may help us to predict viral spillovers into new hosts and discuss future directions for the field.
Arinjay Banerjee; Michelle L. Baker; Kirsten Kulcsar; Vikram Misra; Raina Plowright; Karen Mossman. Novel Insights Into Immune Systems of Bats. Frontiers in Immunology 2020, 11, 26 .
AMA StyleArinjay Banerjee, Michelle L. Baker, Kirsten Kulcsar, Vikram Misra, Raina Plowright, Karen Mossman. Novel Insights Into Immune Systems of Bats. Frontiers in Immunology. 2020; 11 ():26.
Chicago/Turabian StyleArinjay Banerjee; Michelle L. Baker; Kirsten Kulcsar; Vikram Misra; Raina Plowright; Karen Mossman. 2020. "Novel Insights Into Immune Systems of Bats." Frontiers in Immunology 11, no. : 26.
Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and is listed in the World Health Organization’s blueprint of priority diseases that need immediate research. Camels are reservoirs of this virus, and the virus spills over into humans through direct contact with camels. Human-to-human transmission and travel-associated cases have been identified as well. Limited studies have characterized the molecular pathogenesis of MERS-CoV. Most studies have used ectopic expression of viral proteins to characterize MERS-CoV and its ability to modulate antiviral responses in human cells. Studies with live virus are limited, largely due to the requirement of high containment laboratories. In this review, we have summarized current studies on MERS-CoV molecular pathogenesis and have mentioned some recent strategies that are being developed to control MERS-CoV infection. Multiple antiviral molecules with the potential to inhibit MERS-CoV infection by disrupting virus-receptor interactions are being developed and tested. Although human vaccine candidates are still being developed, a candidate camel vaccine is being tested for efficacy. Combination of supportive treatment with interferon and antivirals is also being explored. New antiviral molecules that inhibit MERS-CoV and host cell receptor interaction may become available in the future. Additional studies are required to identify and characterize the pathogenesis of MERS-CoV EMC/2012 and other circulating strains. An effective MERS-CoV vaccine, for humans and/or camels, along with an efficient combination antiviral therapy may help us prevent future MERS cases.
Arinjay Banerjee; Kaushal Baid; Karen Mossman. Molecular Pathogenesis of Middle East Respiratory Syndrome (MERS) Coronavirus. Current Clinical Microbiology Reports 2019, 6, 139 -147.
AMA StyleArinjay Banerjee, Kaushal Baid, Karen Mossman. Molecular Pathogenesis of Middle East Respiratory Syndrome (MERS) Coronavirus. Current Clinical Microbiology Reports. 2019; 6 (3):139-147.
Chicago/Turabian StyleArinjay Banerjee; Kaushal Baid; Karen Mossman. 2019. "Molecular Pathogenesis of Middle East Respiratory Syndrome (MERS) Coronavirus." Current Clinical Microbiology Reports 6, no. 3: 139-147.
Insectivorous bats are speculated to be ancestral hosts of Middle-East respiratory syndrome (MERS) coronavirus (CoV). MERS-CoV causes disease in humans with thirty-five percent fatality, and has evolved proteins that counteract human antiviral responses. Since bats experimentally infected with MERS-CoV do not develop signs of disease, we tested the hypothesis that MERS-CoV would replicate less efficiently in bat cells than in human cells because of its inability to subvert antiviral responses in bat cells. We infected human and bat (Eptesicus fuscus) cells with MERS-CoV and observed that the virus grew to higher titers in human cells. MERS-CoV also effectively suppressed the antiviral interferon beta (IFNβ) response in human cells, unlike in bat cells. To determine if IRF3, a critical mediator of the interferon response, also regulated the response in bats, we examined the response of IRF3 to poly(I:C), a synthetic analogue of viral double-stranded RNA. We observed that bat IRF3 responded to poly(I:C) by nuclear translocation and post-translational modifications, hallmarks of IRF3 activation. Suppression of IRF3 by small-interfering RNA (siRNA) demonstrated that IRF3 was critical for poly(I:C) and MERS-CoV induced induction of IFNβ in bat cells. Our study demonstrates that innate antiviral signaling in E. fuscus bat cells is resistant to MERS-CoV-mediated subversion.
Arinjay Banerjee; Darryl Falzarano; Noreen Rapin; Jocelyne Lew; Vikram Misra. Interferon Regulatory Factor 3-Mediated Signaling Limits Middle-East Respiratory Syndrome (MERS) Coronavirus Propagation in Cells from an Insectivorous Bat. Viruses 2019, 11, 152 .
AMA StyleArinjay Banerjee, Darryl Falzarano, Noreen Rapin, Jocelyne Lew, Vikram Misra. Interferon Regulatory Factor 3-Mediated Signaling Limits Middle-East Respiratory Syndrome (MERS) Coronavirus Propagation in Cells from an Insectivorous Bat. Viruses. 2019; 11 (2):152.
Chicago/Turabian StyleArinjay Banerjee; Darryl Falzarano; Noreen Rapin; Jocelyne Lew; Vikram Misra. 2019. "Interferon Regulatory Factor 3-Mediated Signaling Limits Middle-East Respiratory Syndrome (MERS) Coronavirus Propagation in Cells from an Insectivorous Bat." Viruses 11, no. 2: 152.
Bats are speculated to be reservoirs of several emerging viruses including coronaviruses (CoVs) that cause serious disease in humans and agricultural animals. These include CoVs that cause severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), porcine epidemic diarrhea (PED) and severe acute diarrhea syndrome (SADS). Bats that are naturally infected or experimentally infected do not demonstrate clinical signs of disease. These observations have allowed researchers to speculate that bats are the likely reservoirs or ancestral hosts for several CoVs. In this review, we follow the CoV outbreaks that are speculated to have originated in bats. We review studies that have allowed researchers to identify unique adaptation in bats that may allow them to harbor CoVs without severe disease. We speculate about future studies that are critical to identify how bats can harbor multiple strains of CoVs and factors that enable these viruses to “jump” from bats to other mammals. We hope that this review will enable readers to identify gaps in knowledge that currently exist and initiate a dialogue amongst bat researchers to share resources to overcome present limitations.
Arinjay Banerjee; Kirsten Kulcsar; Vikram Misra; Matthew Frieman; Karen Mossman. Bats and Coronaviruses. Viruses 2019, 11, 41 .
AMA StyleArinjay Banerjee, Kirsten Kulcsar, Vikram Misra, Matthew Frieman, Karen Mossman. Bats and Coronaviruses. Viruses. 2019; 11 (1):41.
Chicago/Turabian StyleArinjay Banerjee; Kirsten Kulcsar; Vikram Misra; Matthew Frieman; Karen Mossman. 2019. "Bats and Coronaviruses." Viruses 11, no. 1: 41.
Commentary: Phyllostomid bat microbiome composition is associated to host phylogeny and feeding strategies
Arinjay Banerjee; Edel Pérez-López; Karen Mossman. Commentary: Phyllostomid bat microbiome composition is associated to host phylogeny and feeding strategies. Frontiers in Microbiology 2018, 9, 2863 .
AMA StyleArinjay Banerjee, Edel Pérez-López, Karen Mossman. Commentary: Phyllostomid bat microbiome composition is associated to host phylogeny and feeding strategies. Frontiers in Microbiology. 2018; 9 ():2863.
Chicago/Turabian StyleArinjay Banerjee; Edel Pérez-López; Karen Mossman. 2018. "Commentary: Phyllostomid bat microbiome composition is associated to host phylogeny and feeding strategies." Frontiers in Microbiology 9, no. : 2863.