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Article ; Online: Human Susceptibility to Influenza Infection and Severe Disease.

Mettelman, Robert C / Thomas, Paul G

Cold Spring Harbor perspectives in medicine

2021 Volume 11, Issue 5

Abstract: Influenza viruses are a persistent threat to global human health. Increased susceptibility to infection and the risk factors associated with progression to severe influenza-related disease are determined by a multitude of viral, host, and environmental ... ...

Abstract	Influenza viruses are a persistent threat to global human health. Increased susceptibility to infection and the risk factors associated with progression to severe influenza-related disease are determined by a multitude of viral, host, and environmental conditions. Decades of epidemiologic research have broadly defined high-risk groups, while new genomic association studies have identified specific host factors impacting an individual's response to influenza. Here, we review and highlight both human susceptibility to influenza infection and the conditions that lead to severe influenza disease.
MeSH term(s)	Disease Susceptibility ; Host-Pathogen Interactions ; Humans ; Influenza, Human/physiopathology ; Patient Acuity
Language	English
Publishing date	2021-05-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	2157-1422
ISSN (online)	2157-1422
DOI	10.1101/cshperspect.a038711
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Article ; Online: Mucosal immune responses to infection and vaccination in the respiratory tract.

Mettelman, Robert C / Allen, E Kaitlynn / Thomas, Paul G

Immunity

2022 Volume 55, Issue 5, Page(s) 749–780

Abstract: The lungs are constantly exposed to inhaled debris, allergens, pollutants, commensal or pathogenic microorganisms, and respiratory viruses. As a result, innate and adaptive immune responses in the respiratory tract are tightly regulated and are in ... ...

Abstract	The lungs are constantly exposed to inhaled debris, allergens, pollutants, commensal or pathogenic microorganisms, and respiratory viruses. As a result, innate and adaptive immune responses in the respiratory tract are tightly regulated and are in continual flux between states of enhanced pathogen clearance, immune-modulation, and tissue repair. New single-cell-sequencing techniques are expanding our knowledge of airway cellular complexity and the nuanced connections between structural and immune cell compartments. Understanding these varied interactions is critical in treatment of human pulmonary disease and infections and in next-generation vaccine design. Here, we review the innate and adaptive immune responses in the lung and airways following infection and vaccination, with particular focus on influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The ongoing SARS-CoV-2 pandemic has put pulmonary research firmly into the global spotlight, challenging previously held notions of respiratory immunity and helping identify new populations at high risk for respiratory distress.
MeSH term(s)	COVID-19/prevention & control ; Humans ; Immunity, Innate ; Immunity, Mucosal ; Lung ; SARS-CoV-2 ; Vaccination
Language	English
Publishing date	2022-05-24
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2022.04.013
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Article ; Online: Resolving SARS-CoV-2 CD4

Pogorelyy, Mikhail V / Rosati, Elisa / Minervina, Anastasia A / Mettelman, Robert C / Scheffold, Alexander / Franke, Andre / Bacher, Petra / Thomas, Paul G

Cell reports. Medicine

2022 Volume 3, Issue 8, Page(s) 100697

Abstract: The current strategy to detect immunodominant T cell responses focuses on the antigen, employing large peptide pools to screen for functional cell activation. However, these approaches are labor and sample intensive and scale poorly with increasing size ... ...

Abstract	The current strategy to detect immunodominant T cell responses focuses on the antigen, employing large peptide pools to screen for functional cell activation. However, these approaches are labor and sample intensive and scale poorly with increasing size of the pathogen peptidome. T cell receptors (TCRs) recognizing the same epitope frequently have highly similar sequences, and thus, the presence of large sequence similarity clusters in the TCR repertoire likely identify the most public and immunodominant responses. Here, we perform a meta-analysis of large, publicly available single-cell and bulk TCR datasets from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals to identify public CD4
MeSH term(s)	CD4-Positive T-Lymphocytes/chemistry ; COVID-19 ; Epitopes/analysis ; Humans ; Receptors, Antigen, T-Cell/genetics ; SARS-CoV-2 ; T-Cell Antigen Receptor Specificity
Chemical Substances	Epitopes ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2022-07-01
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2022.100697
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Article ; Online: Generating and evaluating type I interferon receptor-deficient and feline TMPRSS2-expressing cells for propagating serotype I feline infectious peritonitis virus.

Mettelman, Robert C / O'Brien, Amornrat / Whittaker, Gary R / Baker, Susan C

Virology

2019 Volume 537, Page(s) 226–236

Abstract: Feline coronavirus infection can progress to a fatal infectious peritonitis, which is a widespread feline disease without an effective vaccine. Generating feline cells with reduced ability to respond to interferon (IFN) is an essential step facilitating ... ...

Abstract	Feline coronavirus infection can progress to a fatal infectious peritonitis, which is a widespread feline disease without an effective vaccine. Generating feline cells with reduced ability to respond to interferon (IFN) is an essential step facilitating isolation of new candidate vaccine strains. Here, we describe the use of Crispr/Cas technology to disrupt type I IFN signaling in two feline cell lines, AK-D and Fcwf-4 CU, and evaluate the replication kinetics of a serotype I feline infectious peritonitis virus (FIPV) within these cells. We report that polyclonal cell populations and a clonal isolate, termed Fcwf-4 IRN, exhibited significantly diminished IFN-responsiveness and allowed FIPV replication kinetics comparable to parental cells. Furthermore, we demonstrate that replication of FIPV is enhanced by ectopic expression of a host serine protease, TMPRSS2, in these cells. We discuss the potential of these cells for isolating new clinical strains and for propagating candidate vaccine strains of FIPV.
MeSH term(s)	Animals ; Cats ; Cell Line ; Coronavirus, Feline/growth & development ; Coronavirus, Feline/immunology ; Gene Editing ; Receptor, Interferon alpha-beta/deficiency ; Receptors, Virus/biosynthesis ; Receptors, Virus/genetics ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/genetics ; Serine Endopeptidases/biosynthesis ; Serine Endopeptidases/genetics ; Virus Cultivation/methods ; Virus Replication
Chemical Substances	Receptors, Virus ; Recombinant Proteins ; Receptor, Interferon alpha-beta (156986-95-7) ; Serine Endopeptidases (EC 3.4.21.-)
Keywords	covid19
Language	English
Publishing date	2019-08-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2019.08.030
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Article ; Online: Baseline innate and T cell populations are correlates of protection against symptomatic influenza virus infection independent of serology.

Mettelman, Robert C / Souquette, Aisha / Van de Velde, Lee-Ann / Vegesana, Kasi / Allen, E Kaitlynn / Kackos, Christina M / Trifkovic, Sanja / DeBeauchamp, Jennifer / Wilson, Taylor L / St James, Deryn G / Menon, Smrithi S / Wood, Timothy / Jelley, Lauren / Webby, Richard J / Huang, Q Sue / Thomas, Paul G

Nature immunology

2023 Volume 24, Issue 9, Page(s) 1511–1526

Abstract: Evidence suggests that innate and adaptive cellular responses mediate resistance to the influenza virus and confer protection after vaccination. However, few studies have resolved the contribution of cellular responses within the context of preexisting ... ...

Abstract	Evidence suggests that innate and adaptive cellular responses mediate resistance to the influenza virus and confer protection after vaccination. However, few studies have resolved the contribution of cellular responses within the context of preexisting antibody titers. Here, we measured the peripheral immune profiles of 206 vaccinated or unvaccinated adults to determine how baseline variations in the cellular and humoral immune compartments contribute independently or synergistically to the risk of developing symptomatic influenza. Protection correlated with diverse and polyfunctional CD4
MeSH term(s)	Adult ; Humans ; Influenza, Human ; CD8-Positive T-Lymphocytes ; Orthomyxoviridae Infections ; Communicable Diseases ; Orthomyxoviridae
Language	English
Publishing date	2023-08-17
Publishing country	United States
Document type	Journal Article ; 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/s41590-023-01590-2
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Zs.A 5294: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Analysis of Coronavirus Temperature-Sensitive Mutants Reveals an Interplay between the Macrodomain and Papain-Like Protease Impacting Replication and Pathogenesis.

Deng, Xufang / Mettelman, Robert C / O'Brien, Amornrat / Thompson, John A / O'Brien, Timothy E / Baker, Susan C

Journal of virology

2019 Volume 93, Issue 12

Abstract: Analysis of temperature-sensitive (ts) mutant viruses is a classic method allowing researchers to identify genetic loci involved in viral replication and pathogenesis. Here, we report genetic analysis of a ts strain of mouse hepatitis virus (MHV), tsNC11, ...

Abstract	Analysis of temperature-sensitive (ts) mutant viruses is a classic method allowing researchers to identify genetic loci involved in viral replication and pathogenesis. Here, we report genetic analysis of a ts strain of mouse hepatitis virus (MHV), tsNC11, focusing on the role of mutations in the macrodomain (MAC) and the papain-like protease 2 (PLP2) domain of nonstructural protein 3 (nsp3), a component of the viral replication complex. Using MHV reverse genetics, we generated a series of mutant viruses to define the contributions of macrodomain- and PLP2-specific mutations to the ts phenotype. Viral replication kinetics and efficiency-of-plating analysis performed at permissive and nonpermissive temperatures revealed that changes in the macrodomain alone were both necessary and sufficient for the ts phenotype. Interestingly, mutations in the PLP2 domain were not responsible for the temperature sensitivity but did reduce the frequency of reversion of macrodomain mutants. Coimmunoprecipitation studies are consistent with an interaction between the macrodomain and PLP2. Expression studies of the macrodomain-PLP2 portion of nsp3 indicate that the ts mutations enhance proteasome-mediated degradation of the protein. Furthermore, we found that during virus infection, the replicase proteins containing the MAC and PLP2 mutations were more rapidly degraded at the nonpermissive temperature than were the wild-type proteins. Importantly, we show that the macrodomain and PLP2 mutant viruses trigger production of type I interferon
MeSH term(s)	Animals ; Cell Line ; Coronavirus/metabolism ; Coronavirus Infections/metabolism ; HEK293 Cells ; Humans ; Immunity, Innate/immunology ; Interferon Type I/metabolism ; Mice ; Murine hepatitis virus/genetics ; Papain/genetics ; Papain/metabolism ; Peptide Hydrolases/metabolism ; Protein Domains ; Temperature ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/metabolism ; Virulence Factors/metabolism ; Virus Replication/genetics
Chemical Substances	Interferon Type I ; Viral Nonstructural Proteins ; Virulence Factors ; Peptide Hydrolases (EC 3.4.-) ; Papain (EC 3.4.22.2) ; papain-like protease, Coronavirus (EC 3.4.22.2)
Keywords	covid19
Language	English
Publishing date	2019-05-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02140-18
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Zs.A 609: Show issues

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Article: Use of Centers for Disease Control and Prevention Gravid Trap in Catch Basins: Proof-Of-Concept Trials.

Miller, Nicholas / Mettelman, Robert C / Baker, Susan C / Harbison, Justin E

Journal of the American Mosquito Control Association

2015 Volume 31, Issue 2, Page(s) 196–199

Abstract: Gravid traps are commonly used by mosquito control agencies to collect local populations of Culex pipiens, which are then tested for the presence of West Nile virus. Culex pipiens adults disperse a relatively short distance (~2.5 km) from their breeding ... ...

Abstract	Gravid traps are commonly used by mosquito control agencies to collect local populations of Culex pipiens, which are then tested for the presence of West Nile virus. Culex pipiens adults disperse a relatively short distance (~2.5 km) from their breeding site, so it can be challenging to position a sufficient number of gravid traps to accurately monitor these mosquitoes in large urban areas. As placement of these traps is often limited to locations out of public?view, the potential for placing these traps belowground in commonly found storm-water catch basins was investigated. We compared the numbers of mosquitoes isolated in the Centers for Disease Control and Prevention (CDC) gravid traps placed aboveground with various types of CDC gravid traps placed in nearby catch basins. We found that the gravid traps placed in catch basins collected significantly fewer Culex pipiens females as compared to the aboveground traps. However, the 2 types of catch basin traps continued to function and collect mosquitoes despite heavy rainfall and runoff, demonstrating their utility for sample collection in an urban setting. The potential advantages and disadvantages of using catch basins for the placement of CDC gravid traps are discussed.
MeSH term(s)	Animals ; Centers for Disease Control and Prevention (U.S.) ; Culex/physiology ; Female ; Mosquito Control/methods ; Time Factors ; United States
Language	English
Publishing date	2015-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	632618-3
ISSN	8756-971X
ISSN	8756-971X
DOI	10.2987/14-6470R
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Article ; Online: Characterizing replication kinetics and plaque production of type I feline infectious peritonitis virus in three feline cell lines.

O'Brien, Amornrat / Mettelman, Robert C / Volk, Aaron / André, Nicole M / Whittaker, Gary R / Baker, Susan C

Virology

2018 Volume 525, Page(s) 1–9

Abstract: Investigating type I feline coronaviruses (FCoVs) in tissue culture is critical for understanding the basic virology, pathogenesis, and virus-host interactome of these important veterinary pathogens. This has been a perennial challenge as type I FCoV ... ...

Abstract	Investigating type I feline coronaviruses (FCoVs) in tissue culture is critical for understanding the basic virology, pathogenesis, and virus-host interactome of these important veterinary pathogens. This has been a perennial challenge as type I FCoV strains do not easily adapt to cell culture. Here we characterize replication kinetics and plaque formation of a model type I strain FIPV Black in Fcwf-4 cells established at Cornell University (Fcwf-4 CU). We determined that maximum virus titers (>10
MeSH term(s)	Animals ; Cats ; Cell Line ; Coronavirus, Feline/physiology ; Viral Plaque Assay/veterinary ; Virus Cultivation/methods ; Virus Replication/physiology
Keywords	covid19
Language	English
Publishing date	2018-09-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2018.08.022
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Article ; Online: Structure-Guided Mutagenesis Alters Deubiquitinating Activity and Attenuates Pathogenesis of a Murine Coronavirus.

Deng, Xufang / Chen, Yafang / Mielech, Anna M / Hackbart, Matthew / Kesely, Kristina R / Mettelman, Robert C / O'Brien, Amornrat / Chapman, Mackenzie E / Mesecar, Andrew D / Baker, Susan C

Journal of virology

2020 Volume 94, Issue 11

Abstract: Coronaviruses express a multifunctional papain-like protease, termed papain-like protease 2 (PLP2). PLP2 acts as a protease that cleaves the viral replicase polyprotein and as a deubiquitinating (DUB) enzyme which removes ubiquitin (Ub) moieties from ... ...

Abstract	Coronaviruses express a multifunctional papain-like protease, termed papain-like protease 2 (PLP2). PLP2 acts as a protease that cleaves the viral replicase polyprotein and as a deubiquitinating (DUB) enzyme which removes ubiquitin (Ub) moieties from ubiquitin-conjugated proteins. Previous
MeSH term(s)	Amino Acid Sequence ; Animals ; Coronavirus Infections/virology ; Host-Pathogen Interactions ; Interferon Type I/metabolism ; Macrophages/immunology ; Macrophages/metabolism ; Macrophages/virology ; Mice ; Models, Molecular ; Murine hepatitis virus/pathogenicity ; Murine hepatitis virus/physiology ; Mutagenesis ; Protein Conformation ; Structure-Activity Relationship ; Ubiquitination ; Viral Proteins/chemistry ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virulence ; Virus Replication
Chemical Substances	Interferon Type I ; Viral Proteins
Keywords	covid19
Language	English
Publishing date	2020-05-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01734-19
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Article: SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells.

medRxiv : the preprint server for health sciences

2022

Abstract: Although mRNA vaccine efficacy against severe COVID-19 remains high, variant emergence and breakthrough infections have changed vaccine policy to include booster immunizations. However, the effect of diverse and repeated antigen exposures on SARS-CoV-2 ... ...

Abstract	Although mRNA vaccine efficacy against severe COVID-19 remains high, variant emergence and breakthrough infections have changed vaccine policy to include booster immunizations. However, the effect of diverse and repeated antigen exposures on SARS-CoV-2 memory T cells is poorly understood. Here, we utilize DNA-barcoded MHC-multimers combined with scRNAseq and scTCRseq to capture the
Language	English
Publishing date	2022-01-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.07.12.21260227
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