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Article ; Online: Rift Valley Fever.

Kimble, J Brian / Noronha, Leela / Trujillo, Jessie D / Mitzel, Dana / Richt, Juergen A / Wilson, William C

The Veterinary clinics of North America. Food animal practice

2024

Abstract: Rift Valley fever (RVF) is a zoonotic viral disease that affects domestic and wild ruminants such as cattle, sheep, goats, camels, and buffaloes. Rift valley fever virus (RVFV), the causative agent of RVF, can also infect humans. RVFV is an arthropod- ... ...

Abstract	Rift Valley fever (RVF) is a zoonotic viral disease that affects domestic and wild ruminants such as cattle, sheep, goats, camels, and buffaloes. Rift valley fever virus (RVFV), the causative agent of RVF, can also infect humans. RVFV is an arthropod-borne virus (arbovirus) that is primarily spread through the bites of infected mosquitoes or exposure to infected blood. RVFV was first isolated and characterized in the Rift Valley of Kenya in 1931 and is endemic throughout sub-Saharan Africa, including Comoros and Madagascar, the Arabian Peninsula (Saudi Arabia and Yemen), and Mayotte.
Language	English
Publishing date	2024-03-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	286086-7
ISSN	1558-4240 ; 0749-0720
ISSN (online)	1558-4240
ISSN	0749-0720
DOI	10.1016/j.cvfa.2024.01.004
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Article ; Online: Mouse-Adapted SARS-CoV-2 MA10 Strain Displays Differential Pulmonary Tropism and Accelerated Viral Replication, Neurodissemination, and Pulmonary Host Responses in K18-hACE2 Mice.

Thieulent, Côme J / Dittmar, Wellesley / Balasuriya, Udeni B R / Crossland, Nicholas A / Wen, Xue / Richt, Juergen A / Carossino, Mariano

mSphere

2023 Volume 8, Issue 1, Page(s) e0055822

Abstract: Several models were developed to study the pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as ... ...

Abstract	Several models were developed to study the pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as the
MeSH term(s)	Mice ; Humans ; Animals ; SARS-CoV-2 ; COVID-19/pathology ; Angiotensin-Converting Enzyme 2/genetics ; Pandemics ; Lung/pathology ; Virus Replication ; Mice, Transgenic ; Tropism
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; K-18 conjugate
Language	English
Publishing date	2023-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2379-5042
ISSN (online)	2379-5042
DOI	10.1128/msphere.00558-22
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Article: Evolution of Diagnostic Tests for Chronic Wasting Disease, a Naturally Occurring Prion Disease of Cervids.

Haley, Nicholas J / Richt, Jürgen A

Pathogens (Basel, Switzerland)

2017 Volume 6, Issue 3

Abstract: Since chronic wasting disease (CWD) was first identified nearly 50 years ago in a captive mule deer herd in the Rocky Mountains of the United States, it has slowly spread across North America through the natural and anthropogenic movement of cervids and ... ...

Abstract	Since chronic wasting disease (CWD) was first identified nearly 50 years ago in a captive mule deer herd in the Rocky Mountains of the United States, it has slowly spread across North America through the natural and anthropogenic movement of cervids and their carcasses. As the endemic areas have expanded, so has the need for rapid, sensitive, and cost effective diagnostic tests-especially those which take advantage of samples collected antemortem. Over the past two decades, strategies have evolved from the recognition of microscopic spongiform pathology and associated immunohistochemical staining of the misfolded prion protein to enzyme-linked immunoassays capable of detecting the abnormal prion conformer in postmortem samples. In a history that parallels the diagnosis of more conventional infectious agents, both qualitative and real-time amplification assays have recently been developed to detect minute quantities of misfolded prions in a range of biological and environmental samples. With these more sensitive and semi-quantitative approaches has come a greater understanding of the pathogenesis and epidemiology of this disease in the native host. Because the molecular pathogenesis of prion protein misfolding is broadly analogous to the misfolding of other pathogenic proteins, including Aβ and α-synuclein, efforts are currently underway to apply these in vitro amplification techniques towards the diagnosis of Alzheimer's disease, Parkinson's disease, and other proteinopathies. Chronic wasting disease-once a rare disease of Colorado mule deer-now represents one of the most prevalent prion diseases, and should serve as a model for the continued development and implementation of novel diagnostic strategies for protein misfolding disorders in the natural host.
Language	English
Publishing date	2017-08-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens6030035
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Article: Gene editing of pigs to control influenza A virus infections.

Kwon, Taeyong / Artiaga, Bianca L / McDowell, Chester D / Whitworth, Kristin M / Wells, Kevin D / Prather, Randall S / Delhon, Gustavo / Cigan, Mark / White, Stephen N / Retallick, Jamie / Gaudreault, Natasha N / Morozov, Igor / Richt, Juergen A

bioRxiv : the preprint server for biology

2024

Abstract: Proteolytic activation of the hemagglutinin (HA) glycoprotein by host cellular proteases is pivotal for influenza A virus (IAV) infectivity. Highly pathogenic avian influenza viruses possess the multibasic cleavage site of the HA which is cleaved by ... ...

Abstract	Proteolytic activation of the hemagglutinin (HA) glycoprotein by host cellular proteases is pivotal for influenza A virus (IAV) infectivity. Highly pathogenic avian influenza viruses possess the multibasic cleavage site of the HA which is cleaved by ubiquitous proteases, such as furin; in contrast, the monobasic HA motif is recognized and activated by trypsin-like proteases, such as the transmembrane serine protease 2 (TMPRSS2). Here, we aimed to determine the effects of TMPRSS2 on the replication of pandemic H1N1 and H3N2 subtype IAVs in the natural host, the pig. The use of the CRISPR/Cas 9 system led to the establishment of homozygous gene edited (GE)
Language	English
Publishing date	2024-01-16
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.15.575771
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Article ; Online: Raccoons accumulate PrP

Moore, S Jo / Smith, Jodi D / Richt, Jürgen A / Greenlee, Justin J

Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc

2019 Volume 31, Issue 2, Page(s) 200–209

Abstract: Prion diseases are neurodegenerative diseases characterized by the accumulation of misfolded prion protein ( ... ...

Abstract	Prion diseases are neurodegenerative diseases characterized by the accumulation of misfolded prion protein (PrP
MeSH term(s)	Animals ; Blotting, Western ; Brain ; Deer ; Disease Susceptibility ; Mink ; PrPSc Proteins/metabolism ; Prion Diseases/metabolism ; Prion Diseases/veterinary ; Raccoons ; Sheep ; Wasting Disease, Chronic/etiology ; Wasting Disease, Chronic/metabolism
Chemical Substances	PrPSc Proteins
Language	English
Publishing date	2019-01-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	287603-6
ISSN	1943-4936 ; 1040-6387
ISSN (online)	1943-4936
ISSN	1040-6387
DOI	10.1177/1040638718825290
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Article ; Online: Middle East Respiratory Syndrome-Coronavirus Seropositive Bactrian Camels, Mongolia.

Bold, Dashzeveg / van Doremalen, Neeltje / Myagmarsuren, Odonchimeg / Zayat, Batsukh / Munster, Vincent J / Richt, Juergen A

Vector borne and zoonotic diseases (Larchmont, N.Y.)

2020 Volume 21, Issue 2, Page(s) 128–131

Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic disease that was first identified in humans in 2012 in Saudi Arabia. MERS-CoV causes acute and severe respiratory disease in humans. The mortality rate of MERS in humans is ∼35% and > ... ...

Abstract	Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic disease that was first identified in humans in 2012 in Saudi Arabia. MERS-CoV causes acute and severe respiratory disease in humans. The mortality rate of MERS in humans is ∼35% and >800 deaths have been reported globally as of August 2020. Dromedary camels are a natural host of the virus and the source of zoonotic human infection. In experimental studies, Bactrian camels are susceptible to MERS-CoV infection similar to dromedary camels; however, neither the virus, viral RNA, nor virus-specific antibodies were detected in Bactrian camel field samples so far. The aim of our study was to survey Mongolian camels for MERS-CoV-specific antibodies. A total of 180 camel sera, collected in 2016 and 2017, were involved in this survey: 17 of 180 sera were seropositive with an initial enzyme-linked immunosorbent assay (ELISA) test performed at the State Central Veterinary Laboratory in Mongolia. These 17 positive sera plus 53 additional negative sera were sent to the Rocky Mountain Laboratories, NIAID/NIH, and tested for the presence of antibodies with a similar ELISA, an indirect immunofluorescence assay (IFA), and a virus neutralization test (VNT). In these additional tests, a total of 21 of 70 sera were positive with ELISA and 10 sera were positive with IFA; however, none was positive in the VNT. Based on these results, we hypothesize that the ELISA/IFA-positive antibodies are (1) non-neutralizing antibodies or (2) directed against a MERS-CoV-like virus circulating in Bactrian camels in Mongolia.
MeSH term(s)	Animals ; Antibodies, Viral/blood ; Camelus/virology ; Disease Reservoirs/virology ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique, Indirect ; Middle East Respiratory Syndrome Coronavirus/isolation & purification ; Mongolia ; Seroepidemiologic Studies
Chemical Substances	Antibodies, Viral
Keywords	covid19
Language	English
Publishing date	2020-11-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2047199-3
ISSN	1557-7759 ; 1530-3667
ISSN (online)	1557-7759
ISSN	1530-3667
DOI	10.1089/vbz.2020.2669
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Article: Regulatory T Cell-like Response to SARS-CoV-2 in Jamaican Fruit Bats (

Burke, Bradly / Rocha, Savannah M / Zhan, Shijun / Eckley, Miles / Reasoner, Clara / Addetia, Amin / Lewis, Juliette / Fagre, Anna / Charley, Phillida / Richt, Juergen A / Weiss, Susan R / Tjalkens, Ronald B / Veesler, David / Aboellail, Tawfik / Schountz, Tony

bioRxiv : the preprint server for biology

2023

Abstract: Insectivorous Old World horseshoe bats ( : Author summary: Bats are reservoir hosts of many viruses that infect humans, yet little is known about how they host these viruses, principally because of a lack of relevant and susceptible bat experimental ... ...

Abstract	Insectivorous Old World horseshoe bats ( Author summary: Bats are reservoir hosts of many viruses that infect humans, yet little is known about how they host these viruses, principally because of a lack of relevant and susceptible bat experimental infection models. Although SARS-CoV-2 originated in bats, no robust infection models of bats have been established. We determined that Jamaican fruit bats are poorly susceptible to SARS-CoV-2; however, their lungs can be transduced with human ACE2, which renders them susceptible to SARS-CoV-2. Despite robust infection of the lungs and diminishment of pulmonary cellularity, the bats showed no overt signs of disease and cleared the infection after two weeks. Despite clearance of infection, only low-titer antibody responses occurred and only a single bat made neutralizing antibody. Assessment of the CD4
Language	English
Publishing date	2023-02-20
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.13.528205
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Article ; Online: De novo

Thakkar, Ravindra / Agarwal, Dilip K / Ranaweera, Chathuranga B / Ishiguro, Susumu / Conda-Sheridan, Martin / Gaudreault, Natasha N / Richt, Juergen A / Tamura, Masaaki / Comer, Jeffrey

RSC medicinal chemistry

2023 Volume 14, Issue 9, Page(s) 1722–1733

Abstract: Although effective vaccines have been developed against SARS-CoV-2, many regions in the world still have low rates of vaccination and new variants with mutations in the viral spike protein have reduced the effectiveness of most available vaccines and ... ...

Abstract	Although effective vaccines have been developed against SARS-CoV-2, many regions in the world still have low rates of vaccination and new variants with mutations in the viral spike protein have reduced the effectiveness of most available vaccines and treatments. There is an urgent need for a drug to cure this disease and prevent infection. The SARS-CoV-2 virus enters the host cell through protein-protein interaction between the virus's spike protein and the host's angiotensin converting enzyme (ACE2). Using protein design software and molecular dynamics simulations, we have designed a 17-residue peptide (pep39), that binds to the spike protein receptor-binding domain (RBD) and blocks interaction of spike protein with ACE2. We have confirmed the binding activity of the designed peptide for the original spike protein and the delta variant spike protein using micro-cantilever and bio-layer interferometry (BLI) based methods. We also confirmed that pep39 strongly inhibits SARS-CoV-2 virus replication in Vero E6 cells. Taken together these data suggest that a newly designed spike protein RBD blocking peptide pep39 has a potential as a SARS-CoV-2 virus inhibitor.
Language	English
Publishing date	2023-07-31
Publishing country	England
Document type	Journal Article
ISSN	2632-8682
ISSN (online)	2632-8682
DOI	10.1039/d3md00222e
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Article ; Online: Detection of African Swine Fever Virus in

Craig, Anthony F / Schade-Weskott, Mathilde L / Rametse, Thapelo / Heath, Livio / Kriel, Gideon J P / de Klerk-Lorist, Lin-Mari / van Schalkwyk, Louis / Trujillo, Jessie D / Crafford, Jan E / Richt, Juergen A / Swanepoel, Robert

Viruses

2022 Volume 14, Issue 8

Abstract: We investigated the possibility that sylvatic circulation of African swine fever virus (ASFV) in warthogs ... ...

Abstract	We investigated the possibility that sylvatic circulation of African swine fever virus (ASFV) in warthogs and
MeSH term(s)	African Swine Fever/diagnosis ; African Swine Fever/epidemiology ; African Swine Fever Virus/genetics ; Animals ; Nucleic Acids ; Ornithodoros ; South Africa/epidemiology ; Swine
Chemical Substances	Nucleic Acids
Language	English
Publishing date	2022-07-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14081617
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Article ; Online: Regulatory T cell-like response to SARS-CoV-2 in Jamaican fruit bats (Artibeus jamaicensis) transduced with human ACE2.

Burke, Bradly / Rocha, Savannah M / Zhan, Shijun / Eckley, Miles / Reasoner, Clara / Addetia, Amin / Lewis, Juliette / Fagre, Anna / Charley, Phillida A / Richt, Juergen A / Weiss, Susan R / Tjalkens, Ronald B / Veesler, David / Aboellail, Tawfik / Schountz, Tony

PLoS pathogens

2023 Volume 19, Issue 10, Page(s) e1011728

Abstract: Insectivorous Old World horseshoe bats (Rhinolophus spp.) are the likely source of the ancestral SARS-CoV-2 prior to its spillover into humans and causing the COVID-19 pandemic. Natural coronavirus infections of bats appear to be principally confined to ... ...

Abstract	Insectivorous Old World horseshoe bats (Rhinolophus spp.) are the likely source of the ancestral SARS-CoV-2 prior to its spillover into humans and causing the COVID-19 pandemic. Natural coronavirus infections of bats appear to be principally confined to the intestines, suggesting fecal-oral transmission; however, little is known about the biology of SARS-related coronaviruses in bats. Previous experimental challenges of Egyptian fruit bats (Rousettus aegyptiacus) resulted in limited infection restricted to the respiratory tract, whereas insectivorous North American big brown bats (Eptesicus fuscus) showed no evidence of infection. In the present study, we challenged Jamaican fruit bats (Artibeus jamaicensis) with SARS-CoV-2 to determine their susceptibility. Infection was confined to the intestine for only a few days with prominent viral nucleocapsid antigen in epithelial cells, and mononuclear cells of the lamina propria and Peyer's patches, but with no evidence of infection of other tissues; none of the bats showed visible signs of disease or seroconverted. Expression levels of ACE2 were low in the lungs, which may account for the lack of pulmonary infection. Bats were then intranasally inoculated with a replication-defective adenovirus encoding human ACE2 and 5 days later challenged with SARS-CoV-2. Viral antigen was prominent in lungs for up to 14 days, with loss of pulmonary cellularity during this time; however, the bats did not exhibit weight loss or visible signs of disease. From day 7, bats had low to moderate IgG antibody titers to spike protein by ELISA, and one bat on day 10 had low-titer neutralizing antibodies. CD4+ helper T cells became activated upon ex vivo recall stimulation with SARS-CoV-2 nucleocapsid peptide library and exhibited elevated mRNA expression of the regulatory T cell cytokines interleukin-10 and transforming growth factor-β, which may have limited inflammatory pathology. Collectively, these data show that Jamaican fruit bats are poorly susceptible to SARS-CoV-2 but that expression of human ACE2 in their lungs leads to robust infection and an adaptive immune response with low-titer antibodies and a regulatory T cell-like response that may explain the lack of prominent inflammation in the lungs. This model will allow for insight of how SARS-CoV-2 infects bats and how bat innate and adaptive immune responses engage the virus without overt clinical disease.
MeSH term(s)	Animals ; Humans ; Chiroptera ; SARS-CoV-2 ; Angiotensin-Converting Enzyme 2 ; Pandemics ; Jamaica ; T-Lymphocytes, Regulatory ; COVID-19
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2023-10-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011728
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