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Article: FELINE CORONAVIRUS AND FELINE INFECTIOUS PERITONITIS IN NONDOMESTIC FELID SPECIES.

Stout, Alison E / André, Nicole M / Whittaker, Gary R

Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians

2021 Volume 52, Issue 1, Page(s) 14–27

Abstract: Feline coronavirus (FCoV) is reported worldwide and known to cause disease in domestic and nondomestic felid species. Although FCoV often results in mild to inapparent disease, a small subset of cats succumb to the fatal, systemic disease feline ... ...

Abstract	Feline coronavirus (FCoV) is reported worldwide and known to cause disease in domestic and nondomestic felid species. Although FCoV often results in mild to inapparent disease, a small subset of cats succumb to the fatal, systemic disease feline infectious peritonitis (FIP). An outbreak of FIP in Cheetahs (
MeSH term(s)	Africa/epidemiology ; Animals ; Animals, Wild ; Animals, Zoo ; Brazil/epidemiology ; Cats ; Coronavirus, Feline/pathogenicity ; Europe/epidemiology ; Felidae/virology ; Feline Infectious Peritonitis/epidemiology ; Feline Infectious Peritonitis/mortality ; Feline Infectious Peritonitis/virology ; Female ; Male ; North America/epidemiology ; Seroepidemiologic Studies
Language	English
Publishing date	2021-04-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2174930-9
ISSN	1937-2825 ; 1042-7260
ISSN (online)	1937-2825
ISSN	1042-7260
DOI	10.1638/2020-0134
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Unsaturated fatty acid alters the immune response in non-small cell lung adenocarcinoma through regulation of HMGB1 trafficking.

Cole-Skinner, Breanna / Andre, Nicole M / Blankenheim, Zachary / Root, Kate / Simmons, Glenn E

bioRxiv : the preprint server for biology

2023

Abstract: Cancer cell evasion of the immune response is critical to cancer development and metastases. The ability of clinicians to kickstart the immune system to target these rogue cells is an ever-growing area of research and medicine. In this study, we delved ... ...

Abstract	Cancer cell evasion of the immune response is critical to cancer development and metastases. The ability of clinicians to kickstart the immune system to target these rogue cells is an ever-growing area of research and medicine. In this study, we delved into the relationship between lipid metabolism, High Mobility Group Box 1 protein (HMGB1), and immune regulation within non-small cell lung adenocarcinoma (NSCLC), shedding light on novel therapeutic avenues and potential personalized approaches for patients. We found that the expression of stearoyl CoA desaturase 1 (SCD1) was decreased in NSCLC tumors compared to normal tissues. This emphasized the critical role of lipid metabolism in tumor progression. Interestingly, monounsaturated fatty acid (MUFA) availability impacted the expression of programmed death receptor ligand -1 (PD-L1), a pivotal immune checkpoint target in lung cancer cells and immune cells, suggesting a novel approach to modulating the immune response. This study uncovered a complex interplay between HMGB1, SCD1, and PD-L1, influencing the immunological sensitivity of tumors. Our work underscores the importance of understanding the intricate relationships between lipid metabolism and immune modulation to develop more effective NSCLC treatments and personalized therapies. As we continue to explore these connections, we hope to contribute to the ever-evolving field of cancer research, improving patient outcomes and advancing precision medicine in NSCLC.
Language	English
Publishing date	2023-11-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.08.566231
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Feline infectious peritonitis virus-associated rhinitis in a cat.

André, Nicole M / Miller, Andrew D / Whittaker, Gary R

JFMS open reports

2020 Volume 6, Issue 1, Page(s) 2055116920930582

Abstract: Case summary: This report describes a cat with initial respiratory signs prior to developing fulminant feline infectious peritonitis (FIP) after adoption from an animal shelter. Histologic examination of the tissues revealed typical lesions associated ... ...

Abstract	Case summary: This report describes a cat with initial respiratory signs prior to developing fulminant feline infectious peritonitis (FIP) after adoption from an animal shelter. Histologic examination of the tissues revealed typical lesions associated with FIP in the lung, liver, large intestine and small intestine. Histologic examination of the nasal cavity revealed pyogranulomatous rhinitis. Immunohistochemistry with monoclonal antibody FIPV3-70 targeting FIP antigen in macrophages confirmed FIP and molecular analysis identified a spike protein mutation (R793S) consistent with the presence of an FIP virus. Pathological changes, immunolabeling and molecular analysis provide evidence that respiratory infection by feline coronavirus is part of the spectrum of FIP-associated disease. Relevance and novel information: This report highlights nasal pathology associated with FIP through a combination of histopathology, immunohistochemistry and molecular characterization of the virus. Our work supports a little-appreciated role of the respiratory tract in FIP.
Keywords	covid19
Language	English
Publishing date	2020-06-23
Publishing country	England
Document type	Case Reports
ZDB-ID	2822177-1
ISSN	2055-1169 ; 2055-1169
ISSN (online)	2055-1169
ISSN	2055-1169
DOI	10.1177/2055116920930582
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Article ; Online: Outbreak of feline infectious peritonitis (FIP) in shelter-housed cats: molecular analysis of the feline coronavirus S1/S2 cleavage site consistent with a 'circulating virulent-avirulent theory' of FIP pathogenesis.

Healey, Eleni A / Andre, Nicole M / Miller, Andrew D / Whittaker, Gary R / Berliner, Elizabeth A

JFMS open reports

2022 Volume 8, Issue 1, Page(s) 20551169221074226

Abstract: Case series summary: This case series describes three shelter-housed cats concurrently diagnosed with feline infectious peritonitis (FIP). The cats were from a cohort of seven surrendered from the site of a house fire. The three cats presented with mild ...

Abstract	Case series summary: This case series describes three shelter-housed cats concurrently diagnosed with feline infectious peritonitis (FIP). The cats were from a cohort of seven surrendered from the site of a house fire. The three cats presented with mild upper respiratory signs. Within 10 days they clinically declined: progressive signs included pyrexia, icterus, lethargy, anorexia and cavitary effusions. Necropsy followed by histopathology and immunohistochemistry confirmed a diagnosis of FIP in all three. Molecular analysis of the causative feline coronavirus (FCoV) revealed varied amino acid alterations in the spike gene both between cats and between sample types in individual cats. A fourth cat from the cohort remained healthy in the shelter but succumbed to FIP 6 weeks post-adoption. Relevance and novel information: This case series places FCoV genetic sequences in the context of clinical signs in a small shelter outbreak. Each of the three cats concurrently developed a slightly different clinical presentation. PCR amplification and genetic sequencing revealed that two cats shared an S1/S2 cleavage site mutation (R790S) previously described to be associated with the development of FIP; one of the cats had an additional S1/S2 cleavage site mutation (R793S). The third cat had a single, identical S1/S2 point mutation (R790G) unique from the other two cats; the R790G mutation has not been previously reported. This case series provides interesting data on point mutations associated with the development of FIP and provides support for a 'circulating virulent-avirulent theory' of FIP pathogenesis in a small shelter outbreak.
Language	English
Publishing date	2022-02-11
Publishing country	England
Document type	Case Reports
ZDB-ID	2822177-1
ISSN	2055-1169 ; 2055-1169
ISSN (online)	2055-1169
ISSN	2055-1169
DOI	10.1177/20551169221074226
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Clinical and Molecular Relationships between COVID-19 and Feline Infectious Peritonitis (FIP).

Sweet, Arjun N / André, Nicole M / Stout, Alison E / Licitra, Beth N / Whittaker, Gary R

Viruses

2022 Volume 14, Issue 3

Abstract: The emergence of severe acute respiratory syndrome 2 (SARS-CoV-2) has led the medical and scientific community to address questions surrounding the pathogenesis and clinical presentation of COVID-19; however, relevant clinical models outside of humans ... ...

Abstract	The emergence of severe acute respiratory syndrome 2 (SARS-CoV-2) has led the medical and scientific community to address questions surrounding the pathogenesis and clinical presentation of COVID-19; however, relevant clinical models outside of humans are still lacking. In felines, a ubiquitous coronavirus, described as feline coronavirus (FCoV), can present as feline infectious peritonitis (FIP)-a leading cause of mortality in young cats that is characterized as a severe, systemic inflammation. The diverse extrapulmonary signs of FIP and rapidly progressive disease course, coupled with a closely related etiologic agent, present a degree of overlap with COVID-19. This paper will explore the molecular and clinical relationships between FIP and COVID-19. While key differences between the two syndromes exist, these similarities support further examination of feline coronaviruses as a naturally occurring clinical model for coronavirus disease in humans.
MeSH term(s)	Animals ; COVID-19/veterinary ; Cats ; Coronavirus, Feline ; Feline Infectious Peritonitis ; SARS-CoV-2
Language	English
Publishing date	2022-02-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14030481
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Intra-host variation in the spike S1/S2 region of a feline coronavirus type-1 in a cat with persistent infection.

Olarte-Castillo, Ximena A / Licitra, Beth N / André, Nicole M / Sierra, Maria A / Mason, Christopher E / Goodman, Laura B / Whittaker, Gary R

bioRxiv : the preprint server for biology

2023

Abstract: Feline coronavirus type 1 (FCoV-1) is widely known for causing feline infectious peritonitis (FIP), a systemic infection that is often fatal, with the virus known as the FIPV biotype. However, subclinical disease also occurs, in which cats may not show ... ...

Abstract	Feline coronavirus type 1 (FCoV-1) is widely known for causing feline infectious peritonitis (FIP), a systemic infection that is often fatal, with the virus known as the FIPV biotype. However, subclinical disease also occurs, in which cats may not show signs and intermittently shed the virus, including in feces, possibly for long periods of time. This virus is known as the FECV biotype. Progression of FECV to FIPV has been linked to several genomic changes, however a specific region of the viral spike protein at the interface of the spike S1 and S2 domains has been especially implicated. In this study, we followed a cat (#576) for six years from 2017, at which time FCoV-1 was detected in feces and conjunctival swabs, until 2022, when the animal was euthanized based on a diagnosis of alimentary small cell lymphoma. Over this time period, the cat was clinically diagnosed with inflammatory bowel disease and chronic rhinitis, and cardiac problems were also suspected. Using hybridization capture targeting the spike (S) gene of FCoV followed by next-generation sequencing, we screened 27 clinical samples. We detected FCoV-1 in 4 samples taken in 2017 (intestine and nasal tissue, feces, and conjunctiva), and 3 samples taken in 2022 (feces, and intestinal and heart tissue), but not in fecal samples taken in 2019 and 2020. Next, we focused on the S1/S2 region within S, which contains the furin cleavage site (FCS), a key regulator of viral transmission and pathogenesis. We show that the FCoV-1 variants obtained from feces in 2017 and 2022 were identical, while the ones from conjunctiva (2017), heart (2022), and intestine (2017 and 2022) were distinct. Sequence comparison of all the variants obtained showed that most of the non-synonymous changes in the S1/S2 region occur within the FCS. In the heart, we found two variants that differed by a single nucleotide, resulting in distinct FCS motifs that differ in one amino acid. It is predicted that one of these FCS motifs will down-regulate spike cleavability. The variant from the conjunctiva (2017) had a 6-nucleotide in-frame insertion that resulted in a longer and more exposed S1/S2 loop, which is predicted to be more accessible to the furin protease. Our studies indicate that FCoV-1 can independently persist in the gastrointestinal tract and heart of a cat over a long period of time without evidence of typical FIP signs, with intermittent viral shedding from the gastrointestinal and respiratory tracts.
Language	English
Publishing date	2023-08-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.31.551356
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Clinical and Molecular Relationships between COVID-19 and Feline Infectious Peritonitis (FIP)

Sweet, Arjun N. / André, Nicole M. / Stout, Alison E. / Licitra, Beth N. / Whittaker, Gary R.

Viruses. 2022 Feb. 26, v. 14, no. 3

2022

Abstract	The emergence of severe acute respiratory syndrome 2 (SARS-CoV-2) has led the medical and scientific community to address questions surrounding the pathogenesis and clinical presentation of COVID-19; however, relevant clinical models outside of humans are still lacking. In felines, a ubiquitous coronavirus, described as feline coronavirus (FCoV), can present as feline infectious peritonitis (FIP)—a leading cause of mortality in young cats that is characterized as a severe, systemic inflammation. The diverse extrapulmonary signs of FIP and rapidly progressive disease course, coupled with a closely related etiologic agent, present a degree of overlap with COVID-19. This paper will explore the molecular and clinical relationships between FIP and COVID-19. While key differences between the two syndromes exist, these similarities support further examination of feline coronaviruses as a naturally occurring clinical model for coronavirus disease in humans.
Keywords	COVID-19 infection ; Feline coronavirus ; Severe acute respiratory syndrome coronavirus 2 ; cats ; disease course ; etiological agents ; feline infectious peritonitis ; inflammation ; models ; mortality ; pathogenesis
Language	English
Dates of publication	2022-0226
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14030481
Database	NAL-Catalogue (AGRICOLA)

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Article: Outbreak of feline infectious peritonitis (FIP) in shelter-housed cats: molecular analysis of the feline coronavirus S1/S2 cleavage site consistent with a ‘circulating virulent–avirulent theory’ of FIP pathogenesis

Healey, Eleni A / Andre, Nicole M / Miller, Andrew D / Whitaker, Gary R / Berliner, Elizabeth A

Journal of feline medicine and surgery open reports. 2022 Feb., v. 8, no. 1

2022

Abstract: This case series describes three shelter-housed cats concurrently diagnosed with feline infectious peritonitis (FIP). The cats were from a cohort of seven surrendered from the site of a house fire. The three cats presented with mild upper respiratory ... ...

Abstract	This case series describes three shelter-housed cats concurrently diagnosed with feline infectious peritonitis (FIP). The cats were from a cohort of seven surrendered from the site of a house fire. The three cats presented with mild upper respiratory signs. Within 10 days they clinically declined: progressive signs included pyrexia, icterus, lethargy, anorexia and cavitary effusions. Necropsy followed by histopathology and immunohistochemistry confirmed a diagnosis of FIP in all three. Molecular analysis of the causative feline coronavirus (FCoV) revealed varied amino acid alterations in the spike gene both between cats and between sample types in individual cats. A fourth cat from the cohort remained healthy in the shelter but succumbed to FIP 6 weeks post-adoption. This case series places FCoV genetic sequences in the context of clinical signs in a small shelter outbreak. Each of the three cats concurrently developed a slightly different clinical presentation. PCR amplification and genetic sequencing revealed that two cats shared an S1/S2 cleavage site mutation (R790S) previously described to be associated with the development of FIP; one of the cats had an additional S1/S2 cleavage site mutation (R793S). The third cat had a single, identical S1/S2 point mutation (R790G) unique from the other two cats; the R790G mutation has not been previously reported. This case series provides interesting data on point mutations associated with the development of FIP and provides support for a ‘circulating virulent–avirulent theory’ of FIP pathogenesis in a small shelter outbreak.
Keywords	Feline coronavirus ; amino acids ; anorexia ; cats ; feline infectious peritonitis ; fever ; genes ; histopathology ; immunohistochemistry ; medicine ; necropsy ; pathogenesis ; point mutation ; surgery
Language	English
Dates of publication	2022-02
Publishing place	SAGE Publications
Document type	Article
ZDB-ID	2822177-1
ISSN	2055-1169
ISSN	2055-1169
DOI	10.1177/20551169221074226
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Structural modeling of 2019-novel coronavirus (nCoV) spike protein reveals a proteolytically-sensitive activation loop as a distinguishing feature compared to SARS-CoV and related SARS-like coronaviruses.

Jaimes, Javier A / Andre, Nicole M / Millet, Jean K / Whittaker, Gary R

ArXiv

2020

Abstract: The 2019 novel coronavirus (2019-nCoV) is currently causing a widespread outbreak centered on Hubei province, China and is a major public health concern. Taxonomically 2019-nCoV is closely related to SARS-CoV and SARS-related bat coronaviruses, and it ... ...

Abstract	The 2019 novel coronavirus (2019-nCoV) is currently causing a widespread outbreak centered on Hubei province, China and is a major public health concern. Taxonomically 2019-nCoV is closely related to SARS-CoV and SARS-related bat coronaviruses, and it appears to share a common receptor with SARS-CoV (ACE-2). Here, we perform structural modeling of the 2019-nCoV spike glycoprotein. Our data provide support for the similar receptor utilization between 2019-nCoV and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains, which we predict to be proteolytically-sensitive. We suggest this loop confers fusion activation and entry properties more in line with MERS-CoV and other coronaviruses, and that the presence of this structural loop in 2019-nCoV may affect virus stability and transmission.
Keywords	covid19
Language	English
Publishing date	2020-02-14
Publishing country	United States
Document type	Preprint
ISSN	2331-8422
ISSN (online)	2331-8422
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Article: Structural modeling of 2019-novel coronavirus (nCoV) spike protein reveals a proteolytically-sensitive activation loop as a distinguishing feature compared to SARS-CoV and related SARS-like coronaviruses.

Jaimes, Javier A / André, Nicole M / Millet, Jean K / Whittaker, Gary R

bioRxiv : the preprint server for biology

2020

Abstract	The 2019 novel coronavirus (2019-nCoV) is currently causing a widespread outbreak centered on Hubei province, China and is a major public health concern. Taxonomically 2019-nCoV is closely related to SARS-CoV and SARS-related bat coronaviruses, and it appears to share a common receptor with SARS-CoV (ACE-2). Here, we perform structural modeling of the 2019-nCoV spike glycoprotein. Our data provide support for the similar receptor utilization between 2019-nCoV and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains, which we predict to be proteolytically-sensitive. We suggest this loop confers fusion activation and entry properties more in line with MERS-CoV and other coronaviruses, and that the presence of this structural loop in 2019-nCoV may affect virus stability and transmission.
Keywords	covid19
Language	English
Publishing date	2020-02-18
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.02.10.942185
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