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  1. Article ; Online: SARS-CoV-2 spike and its adaptable furin cleavage site.

    Whittaker, Gary R

    The Lancet. Microbe

    2021  Volume 2, Issue 10, Page(s) e488–e489

    MeSH term(s) Animals ; COVID-19 ; Chlorocebus aethiops ; Furin ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/genetics ; Vero Cells
    Chemical Substances Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Furin (EC 3.4.21.75)
    Language English
    Publishing date 2021-08-06
    Publishing country England
    Document type Journal Article
    ISSN 2666-5247
    ISSN (online) 2666-5247
    DOI 10.1016/S2666-5247(21)00174-9
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  2. Article ; Online: The SARS-CoV-2 furin cleavage site: natural selection or smoking gun?

    Lubinski, Bailey / Whittaker, Gary R

    The Lancet. Microbe

    2023  Volume 4, Issue 8, Page(s) e570

    MeSH term(s) Animals ; Humans ; Chlorocebus aethiops ; SARS-CoV-2/genetics ; Furin ; COVID-19 ; Vero Cells ; Selection, Genetic
    Chemical Substances Furin (EC 3.4.21.75)
    Language English
    Publishing date 2023-05-23
    Publishing country England
    Document type Letter
    ISSN 2666-5247
    ISSN (online) 2666-5247
    DOI 10.1016/S2666-5247(23)00144-1
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  3. Article ; Online: Backyard zoonoses: The roles of companion animals and peri-domestic wildlife.

    Gamble, Amandine / Olarte-Castillo, Ximena A / Whittaker, Gary R

    Science translational medicine

    2023  Volume 15, Issue 718, Page(s) eadj0037

    Abstract: The spillover of human infectious diseases from animal reservoirs is now well appreciated. However, societal and climate-related changes are affecting the dynamics of such interfaces. In addition to the disruption of traditional wildlife habitats, in ... ...

    Abstract The spillover of human infectious diseases from animal reservoirs is now well appreciated. However, societal and climate-related changes are affecting the dynamics of such interfaces. In addition to the disruption of traditional wildlife habitats, in part because of climate change and human demographics and behavior, there is an increasing zoonotic disease risk from companion animals. This includes such factors as the awareness of animals kept as domestic pets and increasing populations of free-ranging animals in peri-domestic environments. This review presents background and commentary focusing on companion and peri-domestic animals as disease risk for humans, taking into account the human-animal interface and population dynamics between the animals themselves.
    MeSH term(s) Animals ; Humans ; Animals, Wild ; Pets ; Zoonoses/epidemiology ; Communicable Diseases
    Language English
    Publishing date 2023-10-18
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.adj0037
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  4. Article ; Online: An outbreak of a pathogenic canine coronavirus type 2 in captive snow leopards (Panthera uncia) in the U.S, with severe gastrointestinal signs

    Olarte-Castillo, Ximena A. / Whittaker, Gary R.

    bioRxiv

    Abstract: The species alphacoronavirus-1 comprises a set of diverse viruses of cats, dogs, and pigs, and is highly recombinogenic. Within this species, canine coronavirus type 2 (CCoV-2) can infect multiple species of canids, causing a range of clinical outcomes. ... ...

    Abstract The species alphacoronavirus-1 comprises a set of diverse viruses of cats, dogs, and pigs, and is highly recombinogenic. Within this species, canine coronavirus type 2 (CCoV-2) can infect multiple species of canids, causing a range of clinical outcomes. CCoV-2 is genetically related to feline coronavirus type 1 (FCoV-1) and type 2 (FCoV-2), with FCoV-2 being a recombinant genotype of FCoV-1 and CCoV-2. Recently, a novel FCoV (FCoV-23) resulting from recombination with a highly pathogenic (pantropic) CCoV-2 (pCCoV-2) has been identified as the cause of a widespread outbreak among stray/feral cats in Cyprus. To understand the origin of recombinant variants it is crucial to identify hosts that can be infected with viruses in the species alphacoronavirus-1. Experimental evidence indicates that domesticated cats likely play a central role in the emergence of recombinant variants, as they can also be infected with CCoV-2. Wild felids are genetically closely related to domestic cats and may also be susceptible to FCoV and CCoV infection; however, there have been no reports of natural infection with CCoV in domesticated or wild felids. In this study, we retrospectively investigated a localized outbreak of severe enteritis in snow leopards (Panthera uncia) housed in a zoological institute in the U.S. Molecular screening and whole genome sequencing revealed the shedding of CCoV-2 in the feces of the three sick leopards. Phylogenetic analyses of the spike gene revealed it is genetically related to pathogenic variants of CCoV-2 identified in domesticated dogs in the U.S., and to pCCoV-2 CB/05 circulating in Europe. This study provides the first genetic evidence of CCoV-2 infection in a wild felid and highlights the necessity of conducting surveillance of both FCoV and CCoV in domesticated and wild felids.
    Keywords covid19
    Language English
    Publishing date 2024-03-26
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2024.03.25.586607
    Database COVID19

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  5. Article ; Online: Public health surveillance of infectious diseases: beyond point mutations.

    Goodman, Laura B / Whittaker, Gary R

    The Lancet. Microbe

    2021  Volume 2, Issue 2, Page(s) e53–e54

    MeSH term(s) Communicable Diseases/epidemiology ; Humans ; Point Mutation ; Public Health ; Public Health Surveillance
    Language English
    Publishing date 2021-01-14
    Publishing country England
    Document type Journal Article
    ISSN 2666-5247
    ISSN (online) 2666-5247
    DOI 10.1016/S2666-5247(21)00003-3
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  6. Article: Intrinsic furin-mediated cleavability of the spike S1/S2 site from SARS-CoV-2 variant B.1.1.529 (Omicron).

    Lubinski, Bailey / Jaimes, Javier A / Whittaker, Gary R

    bioRxiv : the preprint server for biology

    2022  

    Abstract: The ability of SARS-CoV-2 to be primed for viral entry by the host cell protease furin has become one of the most investigated of the numerous transmission and pathogenicity features of the virus. SARS-CoV-2 The variant B.1.1.529 (Omicron) emerged in ... ...

    Abstract The ability of SARS-CoV-2 to be primed for viral entry by the host cell protease furin has become one of the most investigated of the numerous transmission and pathogenicity features of the virus. SARS-CoV-2 The variant B.1.1.529 (Omicron) emerged in late 2020 and has continued to evolve and is now present in several distinct sub-variants. Here, we analyzed the "furin cleavage site" of the spike protein of SARS-CoV-2 B.1.1.529 (Omicron variant)
    Language English
    Publishing date 2022-07-26
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2022.04.20.488969
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  7. Article ; Online: Going back in time for an antibody to fight COVID-19.

    Whittaker, Gary R / Daniel, Susan

    Nature

    2020  Volume 583, Issue 7815, Page(s) 203–204

    MeSH term(s) Antibodies, Monoclonal ; Betacoronavirus ; Broadly Neutralizing Antibodies ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS Virus ; SARS-CoV-2
    Chemical Substances Antibodies, Monoclonal ; Broadly Neutralizing Antibodies
    Keywords covid19
    Language English
    Publishing date 2020-06-26
    Publishing country England
    Document type News ; Comment
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-020-01816-5
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  8. Article ; Online: Biochemical Characterization of Middle East Respiratory Syndrome Coronavirus Spike Protein Proteolytic Processing.

    Whittaker, Gary R / Millet, Jean K

    Methods in molecular biology (Clifton, N.J.)

    2020  Volume 2099, Page(s) 21–37

    Abstract: The coronavirus spike envelope glycoprotein is an essential viral component that mediates virus entry events. Biochemical assessment of the spike protein is critical for understanding structure-function relationships and the roles of the protein in the ... ...

    Abstract The coronavirus spike envelope glycoprotein is an essential viral component that mediates virus entry events. Biochemical assessment of the spike protein is critical for understanding structure-function relationships and the roles of the protein in the viral life cycle. Coronavirus spike proteins are typically proteolytically processed and activated by host cell enzymes such as trypsin-like proteases, cathepsins, or proprotein-convertases. Analysis of coronavirus spike proteins by western blot allows the visualization and assessment of proteolytic processing by endogenous or exogenous proteases. Here, we present a method based on western blot analysis to investigate spike protein proteolytic cleavage by transient transfection of HEK-293 T cells allowing expression of the spike protein of the highly pathogenic Middle East respiratory syndrome coronavirus in the presence or absence of a cellular trypsin-like transmembrane serine protease, matriptase. Such analysis enables the characterization of cleavage patterns produced by a host protease on a coronavirus spike glycoprotein.
    MeSH term(s) Blotting, Western ; Cell Line ; Coronavirus Infections/virology ; Humans ; Middle East Respiratory Syndrome Coronavirus/metabolism ; Middle East Respiratory Syndrome Coronavirus/pathogenicity ; Protein Processing, Post-Translational ; Proteolysis ; Serine Endopeptidases/metabolism ; Spike Glycoprotein, Coronavirus/metabolism ; Virus Internalization
    Chemical Substances Spike Glycoprotein, Coronavirus ; trypsin-like serine protease ; Serine Endopeptidases (EC 3.4.21.-) ; matriptase (EC 3.4.21.-)
    Keywords covid19
    Language English
    Publishing date 2020-01-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-0211-9_3
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  9. Article: SARS-CoV-2 serosurvey of healthy, privately owned cats presenting to a New York City animal hospital in the early phase of the COVID-19 pandemic (2020-2021).

    Choi, Annette / Stout, Alison E / Rollins, Alicia / Wang, Kally / Guo, Qinghua / Javier, A Jaimes / Kennedy, Monica / Wagner, Bettina / Whittaker, Gary R

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Both domestic and non-domestic cats are now established to be susceptible to infection by SARS-CoV-2, the cause of the ongoing COVID-19 pandemic. While serious disease in cats may occur in some instances, the majority of infections appear to be ... ...

    Abstract Both domestic and non-domestic cats are now established to be susceptible to infection by SARS-CoV-2, the cause of the ongoing COVID-19 pandemic. While serious disease in cats may occur in some instances, the majority of infections appear to be subclinical. Differing prevalence data for SARS-CoV-2 infection of cats have been reported, and are highly context-dependent. Here, we report a retrospective serological survey of cats presented to an animal practice in New York City, located in close proximity to a large medical center that treated the first wave of COVID-19 patients in the US in the Spring of 2020. We sampled 79, mostly indoor, cats between June 2020 to May 2021, the early part of which time the community was under a strict public health "lock-down". Using a highly sensitive and specific fluorescent bead-based multiplex assay, we found an overall prevalence of 13/79 (16%) serologically-positive animals for the study period; however, cats sampled in the Fall of 2020 had a confirmed positive prevalence of 44%. For SARS-CoV-2 seropositive cats, we performed viral neutralization test with live SARS-CoV-2 to additionally confirm presence of SARS-CoV-2 specific antibodies. Of the thirteen seropositive cats, 7/13 (54%) were also positive by virus neutralization, and 2 of seropositive cats had previously documented respiratory signs, with high neutralization titers of 1:1024 and 1:4096; overall however, there was no statistically significant association of SARS-CoV-2 seropositivity with respiratory signs, or with breed, sex or age of the animals. Follow up sampling of cats, while limited in scope, showed that positive serological titers were maintained over time. In comparison, we found an overall confirmed positive prevalence of 51% for feline coronavirus (FCoV), an endemic virus of cats, with 30% confirmed negative for FCoV. We demonstrate the impact of SARS-CoV in a defined feline population during the first wave of SARS-CoV-2 infection of humans, and suggest that human-cat transmission was substantial in our study group. Our data provide a new context for SARS-CoV-2 transmission events across species.
    Language English
    Publishing date 2024-02-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.13.580068
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  10. Article ; Online: Human matriptase/ST 14 proteolytically cleaves H7N9 hemagglutinin and facilitates the activation of influenza A/Shanghai/2/2013 virus in cell culture.

    Whittaker, Gary R / Straus, Marco R

    Influenza and other respiratory viruses

    2019  Volume 14, Issue 2, Page(s) 189–195

    Abstract: Background: Influenza is a zoonotic disease that infects millions of people each year resulting in hundreds of thousands of deaths, and in turn devastating pandemics. Influenza is caused by influenza viruses, including influenza A virus (IAV). There are ...

    Abstract Background: Influenza is a zoonotic disease that infects millions of people each year resulting in hundreds of thousands of deaths, and in turn devastating pandemics. Influenza is caused by influenza viruses, including influenza A virus (IAV). There are many subtypes of IAV but only a few seem to be able to adapt to humans and to cause disease. In 2013, an H7N9 IAV subtype emerged in China that does not cause clinical symptoms in its chicken host but leads to severe infections when transmitted into humans. Since 2013, there have been six epidemic waves of H7N9 with 1567 laboratory-confirmed human infections and 615 deaths. Pathogenicity of IAV is complex, but a crucial feature contributing to virulence is the activation of the hemagglutinin (HA) fusion protein by host proteases that triggers membrane fusion and leads to subsequent virus propagation.
    Methods: 293T, VERO, and MDCK cells were used to conduct Western blot analysis, immunofluorescence assays, and pseudoparticle and live virus infections, and to evaluate H7N9 HA cleavage-activation.
    Results/conclusions: We show that human matriptase/ST 14 is able to cleave H7N9 HA. Cleavage of H7N9 HA expressed in cell culture results in fusogenic HA and syncytia formation. In infection studies with viral pseudoparticles carrying matriptase/ST 14-activated H7N9 HA, we observed a high infectivity of cells. Finally, human matriptase/ST 14 also activated H7N9 live virus which resulted in high infectivity. Our data demonstrate that human matriptase/ST 14 is a likely candidate protease to promote H7N9 infections in humans.
    MeSH term(s) Animals ; Birds ; Chlorocebus aethiops ; Dogs ; HEK293 Cells ; Hemagglutinin Glycoproteins, Influenza Virus/metabolism ; Host-Pathogen Interactions ; Humans ; Influenza A Virus, H7N9 Subtype/growth & development ; Influenza A Virus, H7N9 Subtype/metabolism ; Influenza in Birds/virology ; Influenza, Human/virology ; Madin Darby Canine Kidney Cells ; Serine Endopeptidases/metabolism ; Vero Cells ; Virulence ; Virus Replication
    Chemical Substances Hemagglutinin Glycoproteins, Influenza Virus ; Serine Endopeptidases (EC 3.4.21.-) ; matriptase (EC 3.4.21.-)
    Keywords covid19
    Language English
    Publishing date 2019-12-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2274538-5
    ISSN 1750-2659 ; 1750-2640
    ISSN (online) 1750-2659
    ISSN 1750-2640
    DOI 10.1111/irv.12707
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