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Article ; Online: Defining the role of natural killer cells in COVID-19.

Lee, Madeline J / Blish, Catherine A

2023 Volume 24, Issue 10, Page(s) 1628–1638

Abstract: Natural killer (NK) cells are critical effectors of antiviral immunity. Researchers have therefore sought to characterize the NK cell response to coronavirus disease 2019 (COVID-19) and the virus that causes it, severe acute respiratory syndrome ... ...

Abstract	Natural killer (NK) cells are critical effectors of antiviral immunity. Researchers have therefore sought to characterize the NK cell response to coronavirus disease 2019 (COVID-19) and the virus that causes it, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The NK cells of patients with severe COVID-19 undergo extensive phenotypic and functional changes. For example, the NK cells from critically ill patients with COVID-19 are highly activated and exhausted, with poor cytotoxic function and cytokine production upon stimulation. The NK cell response to SARS-CoV-2 is also modulated by changes induced in virally infected cells, including the ability of a viral peptide to bind HLA-E, preventing NK cells from receiving inhibitory signals, and the downregulation of major histocompatibility complex class I and ligands for the activating receptor NKG2D. These changes have important implications for the ability of infected cells to escape NK cell killing. The implications of these findings for antibody-dependent NK cell activity in COVID-19 are also reviewed. Despite these advances in the understanding of the NK cell response to SARS-CoV-2, there remain critical gaps in our current understanding and a wealth of avenues for future research on this topic.
MeSH term(s)	Humans ; COVID-19/metabolism ; SARS-CoV-2 ; Killer Cells, Natural ; HLA Antigens/metabolism ; Ligands
Chemical Substances	HLA Antigens ; Ligands
Language	English
Publishing date	2023-07-17
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-023-01560-8
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Article ; Online: Maintaining a Robust Pipeline of Future Physician-Scientists.

Blish, Catherine A

The Journal of infectious diseases

2018 Volume 218, Issue suppl_1, Page(s) S40–S43

Abstract: Perhaps the most dramatic finding in the 2014 National Institutes of Health Physician-Scientist Workforce Working Group Report is the aging of the physician-scientist workforce. There are currently 1.6-fold more physician-scientists over the age of 61 ... ...

Abstract	Perhaps the most dramatic finding in the 2014 National Institutes of Health Physician-Scientist Workforce Working Group Report is the aging of the physician-scientist workforce. There are currently 1.6-fold more physician-scientists over the age of 61 than under the age of 50, indicating that our pipeline of physician-scientists is insufficient to maintain current numbers. Several factors likely contribute to this leaky pipeline, including the long training periods, poor compensation during training, diminished funding odds for young investigators, and lack of role models, particularly for women and underrepresented minorities. This perspective will present several ideas for how training programs can play a role in assuring a robust pipeline of future physician scientists.
MeSH term(s)	Age Distribution ; Biomedical Research ; Career Choice ; Education ; Education, Medical ; Female ; Health Workforce/trends ; Humans ; Middle Aged ; Minority Groups ; National Institutes of Health (U.S.) ; Physicians ; Physicians, Women ; Research Personnel/education ; Training Support ; United States
Language	English
Publishing date	2018-08-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiy093
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Article ; Online: Persistence and free chlorine disinfection of human coronaviruses and their surrogates in water.

Zhang, Mengyang / Leong, Michelle Wei / Mitch, William A / Blish, Catherine A / Boehm, Alexandria

Applied and environmental microbiology

2024 Volume 90, Issue 4, Page(s) e0005524

Abstract: The coronavirus disease 2019 pandemic illustrates the importance of understanding the behavior and control of human pathogenic viruses in the environment. Exposure via water (drinking, bathing, and recreation) is a known route of transmission of viruses ... ...

Abstract	The coronavirus disease 2019 pandemic illustrates the importance of understanding the behavior and control of human pathogenic viruses in the environment. Exposure via water (drinking, bathing, and recreation) is a known route of transmission of viruses to humans, but the literature is relatively void of studies on the persistence of many viruses, especially coronaviruses, in water and their susceptibility to chlorine disinfection. To fill that knowledge gap, we evaluated the persistence and free chlorine disinfection of human coronavirus OC43 (HCoV-OC43) and its surrogates, murine hepatitis virus (MHV) and porcine transmissible gastroenteritis virus (TGEV), in drinking water and laboratory buffer using cell culture methods. The decay rate constants of human coronavirus and its surrogates in water varied, depending on virus and water matrix. In drinking water without disinfectant addition, MHV showed the largest decay rate constant (estimate ± standard error, 2.25 ± 0.09 day Importance: This study addresses an important knowledge gap on enveloped virus persistence and disinfection in water. Results have immediate practical applications for shaping evidence-based water policies, particularly in the development of disinfection strategies for pathogenic virus control.
MeSH term(s)	Animals ; Mice ; Swine ; Humans ; Disinfection/methods ; Chlorine/pharmacology ; Drinking Water ; Disinfectants/pharmacology ; Viruses ; Murine hepatitis virus
Chemical Substances	Chlorine (4R7X1O2820) ; Drinking Water ; Disinfectants
Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	223011-2
ISSN	1098-5336 ; 0099-2240
ISSN (online)	1098-5336
ISSN	0099-2240
DOI	10.1128/aem.00055-24
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Article ; Online: Comparative analysis of cell-cell communication at single-cell resolution.

Wilk, Aaron J / Shalek, Alex K / Holmes, Susan / Blish, Catherine A

Nature biotechnology

2023 Volume 42, Issue 3, Page(s) 470–483

Abstract: Inference of cell-cell communication from single-cell RNA sequencing data is a powerful technique to uncover intercellular communication pathways, yet existing methods perform this analysis at the level of the cell type or cluster, discarding single-cell- ...

Abstract	Inference of cell-cell communication from single-cell RNA sequencing data is a powerful technique to uncover intercellular communication pathways, yet existing methods perform this analysis at the level of the cell type or cluster, discarding single-cell-level information. Here we present Scriabin, a flexible and scalable framework for comparative analysis of cell-cell communication at single-cell resolution that is performed without cell aggregation or downsampling. We use multiple published atlas-scale datasets, genetic perturbation screens and direct experimental validation to show that Scriabin accurately recovers expected cell-cell communication edges and identifies communication networks that can be obscured by agglomerative methods. Additionally, we use spatial transcriptomic data to show that Scriabin can uncover spatial features of interaction from dissociated data alone. Finally, we demonstrate applications to longitudinal datasets to follow communication pathways operating between timepoints. Our approach represents a broadly applicable strategy to reveal the full structure of niche-phenotype relationships in health and disease.
MeSH term(s)	Cell Communication/genetics ; Gene Expression Profiling ; Transcriptome ; Single-Cell Analysis
Language	English
Publishing date	2023-05-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1311932-1
ISSN	1546-1696 ; 1087-0156
ISSN (online)	1546-1696
ISSN	1087-0156
DOI	10.1038/s41587-023-01782-z
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Zs.A 2167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Natural Killer Cell Diversity in Viral Infection: Why and How Much?

Blish, Catherine A

Pathogens & immunity

2016 Volume 1, Issue 1, Page(s) 165–192

Abstract: Natural killer cells are a diverse group of innate lymphocytes that are specialized to rapidly respond to cancerous or virus-infected cells. NK cell function is controlled by the integration of signals from activating and inhibitory receptors expressed ... ...

Abstract	Natural killer cells are a diverse group of innate lymphocytes that are specialized to rapidly respond to cancerous or virus-infected cells. NK cell function is controlled by the integration of signals from activating and inhibitory receptors expressed at the cell surface. Variegated expression patterns of these activating and inhibitory receptors at the single cell level leads to a highly diverse NK cell repertoire. Here I review the factors that influence NK cell repertoire diversity and its functional consequences for our ability to fight viruses.
Language	English
Publishing date	2016-08-29
Publishing country	United States
Document type	Journal Article
ISSN	2469-2964
ISSN	2469-2964
DOI	10.20411/pai.v1i1.142
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Article ; Online: Single-cell RNA-seq methods to interrogate virus-host interactions

Ratnasiri, Kalani / Wilk, Aaron J. / Lee, Madeline J. / Khatri, Purvesh / Blish, Catherine A.

Semin Immunopathol. 2023 Jan., v. 45, no. 1, p. 71-89

2023 , Page(s) 71–89

Abstract: The twenty-first century has seen the emergence of many epidemic and pandemic viruses, with the most recent being the SARS-CoV-2-driven COVID-19 pandemic. As obligate intracellular parasites, viruses rely on host cells to replicate and produce progeny, ... ...

Abstract	The twenty-first century has seen the emergence of many epidemic and pandemic viruses, with the most recent being the SARS-CoV-2-driven COVID-19 pandemic. As obligate intracellular parasites, viruses rely on host cells to replicate and produce progeny, resulting in complex virus and host dynamics during an infection. Single-cell RNA sequencing (scRNA-seq), by enabling broad and simultaneous profiling of both host and virus transcripts, represents a powerful technology to unravel the delicate balance between host and virus. In this review, we summarize technological and methodological advances in scRNA-seq and their applications to antiviral immunity. We highlight key scRNA-seq applications that have enabled the understanding of viral genomic and host response heterogeneity, differential responses of infected versus bystander cells, and intercellular communication networks. We expect further development of scRNA-seq technologies and analytical methods, combined with measurements of additional multi-omic modalities and increased availability of publicly accessible scRNA-seq datasets, to enable a better understanding of viral pathogenesis and enhance the development of antiviral therapeutics strategies.
Keywords	COVID-19 infection ; RNA ; cell communication ; data collection ; genomics ; immunity ; pandemic ; pathogenesis ; progeny ; sequence analysis ; therapeutics ; viruses
Language	English
Dates of publication	2023-01
Size	p. 71-89
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
Note	Review
ZDB-ID	2316828-6
ISSN	1863-2300 ; 1863-2297
ISSN (online)	1863-2300
ISSN	1863-2297
DOI	10.1007/s00281-022-00972-2
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 1425: Show issues

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Article: Comparative analysis of cell-cell communication at single-cell resolution.

Wilk, Aaron J / Shalek, Alex K / Holmes, Susan / Blish, Catherine A

bioRxiv : the preprint server for biology

2022

Abstract: Inference of cell-cell communication (CCC) from single-cell RNA-sequencing data is a powerful technique to uncover putative axes of multicellular coordination, yet existing methods perform this analysis at the level of the cell type or cluster, ... ...

Abstract	Inference of cell-cell communication (CCC) from single-cell RNA-sequencing data is a powerful technique to uncover putative axes of multicellular coordination, yet existing methods perform this analysis at the level of the cell type or cluster, discarding single-cell level information. Here we present Scriabin â€" a flexible and scalable framework for comparative analysis of CCC at single-cell resolution. We leverage multiple published datasets to show that Scriabin recovers expected CCC edges and use spatial transcriptomic data, genetic perturbation screens, and direct experimental manipulation of receptor-ligand interactions to validate that the recovered edges are biologically meaningful. We then apply Scriabin to uncover co-expressed programs of CCC from atlas-scale datasets, validating known communication pathways required for maintaining the intestinal stem cell niche and revealing species-specific communication pathways. Finally, we utilize single-cell communication networks calculated using Scriabin to follow communication pathways that operate between timepoints in longitudinal datasets, highlighting bystander cells as important initiators of inflammatory reactions in acute SARS-CoV-2 infection. Our approach represents a broadly applicable strategy to leverage single-cell resolution data maximally toward uncovering CCC circuitry and rich niche-phenotype relationships in health and disease.
Language	English
Publishing date	2022-07-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.02.04.479209
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Article ; Online: The immunology and immunopathology of COVID-19.

Merad, Miriam / Blish, Catherine A / Sallusto, Federica / Iwasaki, Akiko

Science (New York, N.Y.)

2022 Volume 375, Issue 6585, Page(s) 1122–1127

Abstract: Considerable research effort has been made worldwide to decipher the immune response triggered upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, identify the drivers of severe and fatal COVID-19, and understand what leads to ... ...

Abstract	Considerable research effort has been made worldwide to decipher the immune response triggered upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, identify the drivers of severe and fatal COVID-19, and understand what leads to the prolongation of symptoms after disease resolution. We review the results of almost 2 years of COVID-19 immunology research and discuss definitive findings and remaining questions regarding our understanding of COVID-19 pathophysiology. We discuss emerging understanding of differences in immune responses seen in those with and without Long Covid syndrome, also known as post-acute sequelae of SARS-CoV-2. We hope that the knowledge gained from this COVID-19 research will be applied in studies of inflammatory processes involved in critical and chronic illnesses, which remain a major unmet need.
MeSH term(s)	Adaptive Immunity ; Antibodies, Monoclonal/therapeutic use ; Antiviral Agents/therapeutic use ; COVID-19/complications ; COVID-19/immunology ; COVID-19/physiopathology ; COVID-19/therapy ; COVID-19/virology ; Female ; Humans ; Immunity, Innate ; Inflammation ; Male ; Risk Factors ; SARS-CoV-2/immunology ; SARS-CoV-2/physiology ; Severity of Illness Index
Chemical Substances	Antibodies, Monoclonal ; Antiviral Agents
Language	English
Publishing date	2022-03-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abm8108
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Article ; Online: Persistence and Free Chlorine Disinfection of Human Coronaviruses and Their Surrogates in Water

Zhang, Mengyang / Leong, Michelle Wei / Mitch, William A. / Blish, Catherine A. / Boehm, Alexandria

bioRxiv

Abstract: The COVID-19 pandemic illustrates the importance of understanding the behavior and control of human pathogenic viruses in the environment. Exposure via water (drinking, bathing, and recreation) is a known route of transmission of viruses to humans, but ... ...

Abstract	The COVID-19 pandemic illustrates the importance of understanding the behavior and control of human pathogenic viruses in the environment. Exposure via water (drinking, bathing, and recreation) is a known route of transmission of viruses to humans, but the literature is relatively void of studies on the persistence of many viruses, especially coronaviruses, in water and their susceptibility to chlorine disinfection. To fill that knowledge gap, we evaluated the persistence and free chlorine disinfection of human coronavirus OC43 (HCoV-OC43) and its surrogates, murine hepatitis virus (MHV) and porcine transmissible gastroenteritis virus (TGEV), in drinking water and laboratory buffer using cell culture methods. The decay rate constants of human coronavirus and its surrogates in water varied depending on virus and water matrix. In drinking water prior to disinfectant addition, MHV showed the largest decay rate constant (2.25 day-1) followed by HCoV-OC43 (0.99 day<sup>-1</sup>) and TGEV (0.65 day<sup>-1</sup>); while in phosphate buffer, HCoV-OC43 (0.51 day<sup>-1</sup>) had a larger decay rate constant than MHV (0.28 day<sup>-1</sup>) and TGEV (0.24 day<sup>-1</sup>). Upon free chlorine disinfection, the inactivation rates of coronaviruses were independent of free chlorine concentration and not affected by water matrix, though they still varied between viruses. TGEV showed the highest susceptibility to free chlorine disinfection with the inactivation rate constant of 113.50 mg<sup>-1</sup> min<sup>-1</sup> L, followed by MHV (81.33 mg<sup>-1</sup> min<sup>-1</sup> L) and HCoV-OC43 (59.42 mg<sup>-1</sup> min<sup>-1</sup> L).
Keywords	covid19
Language	English
Publishing date	2024-01-20
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.01.16.575911
Database	COVID19

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Article ; Online: Diversification of human NK cells: Lessons from deep profiling.

Wilk, Aaron J / Blish, Catherine A

Journal of leukocyte biology

2018 Volume 103, Issue 4, Page(s) 629–641

Abstract: NK cells are innate lymphocytes with important roles in immunoregulation, immunosurveillance, and cytokine production. Originally defined on the functional basis of their "natural" ability to lyse tumor targets and thought to be a relatively homogeneous ... ...

Abstract	NK cells are innate lymphocytes with important roles in immunoregulation, immunosurveillance, and cytokine production. Originally defined on the functional basis of their "natural" ability to lyse tumor targets and thought to be a relatively homogeneous group of lymphocytes, NK cells possess a remarkable degree of phenotypic and functional diversity due to the combinatorial expression of an array of activating and inhibitory receptors. Diversification of NK cells is multifaceted: mechanisms of NK cell education that promote self-tolerance result in a heterogeneous repertoire that further diversifies upon encounters with viral pathogens. Here, we review the genetic, developmental, and environmental sources of NK cell diversity with a particular focus on deep profiling and single-cell technologies that will enable a more thorough and accurate dissection of this intricate and poorly understood lymphocyte lineage.
MeSH term(s)	Animals ; Environment ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Immunologic Memory ; Killer Cells, Natural/cytology ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism
Language	English
Publishing date	2018-01-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1002/JLB.6RI0917-390R
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