Publications by authors named "Juergen A Richt"

126 Publications

Seasonal Stability of SARS-CoV-2 in Biological Fluids.

Pathogens 2021 Apr 30;10(5). Epub 2021 Apr 30.

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.

The transmission of SARS-CoV-2 occurs by close contact with infected persons through droplets, the inhalation of infectious aerosols, and the exposure to contaminated surfaces. Previously, we determined the virus stability on different types of surfaces under indoor and seasonal climatic conditions. SARS-CoV-2 survived the longest on surfaces under winter conditions, followed by spring/fall and summer conditions, suggesting the seasonal pattern of stability on surfaces. However, under natural conditions, the virus is secreted in various biological fluids from infected humans. In this respect, it remains unclear how long the virus survives in various types of biological fluids. This study explores SARS-CoV-2 stability in virus-spiked human biological fluids under different environmental conditions by determining the virus half-life. The virus was stable for up to 21 days in nasal mucus, sputum, saliva, tear, urine, blood, and semen; it remained infectious significantly longer under winter and spring/fall conditions than under summer conditions. In contrast, the virus was only stable up to 24 h in feces and breast milk. These findings demonstrate the potential risk of infectious biological fluids in SARS-CoV-2 transmission and have implications for its seasonality.
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http://dx.doi.org/10.3390/pathogens10050540DOI Listing
April 2021

Mechanical transmission of SARS-CoV-2 by house flies.

Parasit Vectors 2021 Apr 20;14(1):214. Epub 2021 Apr 20.

Arthropod-Borne Animal Diseases Research Unit, Department of Agriculture, Agricultural Research Service, 1515 College Ave, Manhattan, KS, 66502, USA.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emerged coronavirus that is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 in humans is characterized by a wide range of symptoms that range from asymptomatic to mild or severe illness including death. SARS-CoV-2 is highly contagious and is transmitted via the oral-nasal route through droplets and aerosols, or through contact with contaminated fomites. House flies are known to transmit bacterial, parasitic and viral diseases to humans and animals as mechanical vectors. Previous studies have shown that house flies can mechanically transmit coronaviruses, such as turkey coronavirus; however, the house fly's role in SARS-CoV-2 transmission has not yet been explored. The goal of this work was to investigate the potential of house flies to mechanically transmit SARS-CoV-2. For this purpose, it was determined whether house flies can acquire SARS-CoV-2, harbor live virus and mechanically transmit the virus to naive substrates and surfaces.

Methods: Two independent studies were performed to address the study objectives. In the first study, house flies were tested for infectivity after exposure to SARS-CoV-2-spiked medium or milk. In the second study, environmental samples were tested for infectivity after contact with SARS-CoV-2-exposed flies. During both studies, samples were collected at various time points post-exposure and evaluated by SARS-CoV-2-specific RT-qPCR and virus isolation.

Results: All flies exposed to SARS-CoV-2-spiked media or milk substrates were positive for viral RNA at 4 h and 24 h post-exposure. Infectious virus was isolated only from the flies exposed to virus-spiked milk but not from those exposed to virus-spiked medium. Moreover, viral RNA was detected in environmental samples after contact with SARS-CoV-2 exposed flies, although no infectious virus was recovered from these samples.

Conclusions: Under laboratory conditions, house flies acquired and harbored infectious SARS-CoV-2 for up to 24 h post-exposure. In addition, house flies were able to mechanically transmit SARS-CoV-2 genomic RNA to the surrounding environment up to 24 h post-exposure. Further studies are warranted to determine if house fly transmission occurs naturally and the potential public health implications of such events.
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http://dx.doi.org/10.1186/s13071-021-04703-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056201PMC
April 2021

Seasonal stability of SARS-CoV-2 in biological fluids.

bioRxiv 2021 Apr 8. Epub 2021 Apr 8.

Transmission of SARS-CoV-2 occurs by close contact with infected persons through droplets, the inhalation of infectious aerosols and the exposure to contaminated surface. Previously, we determined the virus stability on different types of surfaces under indoor and seasonal climatic conditions. SARS-CoV-2 survived the longest on surfaces under winter conditions, followed by spring/fall and summer conditions, suggesting the seasonal pattern of stability on surfaces. However, under natural conditions, the virus is secreted in various biological fluids from infected humans. In this respect, it remains unclear how long the virus survives in various types of biological fluids. This study explored the SARS-CoV-2 stability in human biological fluids under different environmental conditions and estimated the half-life. The virus was stable for up to 21 days in nasal mucus, sputum, saliva, tear, urine, blood, and semen; it remained infectious significantly longer under winter and spring/fall conditions than under summer conditions. In contrast, the virus was only stable up to 24 hours in feces and breast milk. These findings demonstrate the potential risk of infectious biological fluids in SARS-CoV-2 transmission and have implications for its seasonality.
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http://dx.doi.org/10.1101/2021.04.07.438866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043457PMC
April 2021

TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation.

Cell 2021 Mar 30. Epub 2021 Mar 30.

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro, and in vivo analyses, we report that topoisomerase 1 (TOP1) inhibition suppresses lethal inflammation induced by SARS-CoV-2. Therapeutic treatment with two doses of topotecan (TPT), an FDA-approved TOP1 inhibitor, suppresses infection-induced inflammation in hamsters. TPT treatment as late as 4 days post-infection reduces morbidity and rescues mortality in a transgenic mouse model. These results support the potential of TOP1 inhibition as an effective host-directed therapy against severe SARS-CoV-2 infection. TPT and its derivatives are inexpensive clinical-grade inhibitors available in most countries. Clinical trials are needed to evaluate the efficacy of repurposing TOP1 inhibitors for severe coronavirus disease 2019 (COVID-19) in humans.
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http://dx.doi.org/10.1016/j.cell.2021.03.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008343PMC
March 2021

Limited Genetic Diversity Detected in Middle East Respiratory Syndrome-Related Coronavirus Variants Circulating in Dromedary Camels in Jordan.

Viruses 2021 03 31;13(4). Epub 2021 Mar 31.

Virus Ecology Section, Laboratory of Virology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT 59840, USA.

Middle East respiratory syndrome-related coronavirus (MERS-CoV) is a persistent zoonotic pathogen with frequent spillover from dromedary camels to humans in the Arabian Peninsula, resulting in limited outbreaks of MERS with a high case-fatality rate. Full genome sequence data from camel-derived MERS-CoV variants show diverse lineages circulating in domestic camels with frequent recombination. More than 90% of the available full MERS-CoV genome sequences derived from camels are from just two countries, the Kingdom of Saudi Arabia (KSA) and United Arab Emirates (UAE). In this study, we employ a novel method to amplify and sequence the partial MERS-CoV genome with high sensitivity from nasal swabs of infected camels. We recovered more than 99% of the MERS-CoV genome from field-collected samples with greater than 500 TCID equivalent per nasal swab from camel herds sampled in Jordan in May 2016. Our subsequent analyses of 14 camel-derived MERS-CoV genomes show a striking lack of genetic diversity circulating in Jordan camels relative to MERS-CoV genome sequences derived from large camel markets in KSA and UAE. The low genetic diversity detected in Jordan camels during our study is consistent with a lack of endemic circulation in these camel herds and reflective of data from MERS outbreaks in humans dominated by nosocomial transmission following a single introduction as reported during the 2015 MERS outbreak in South Korea. Our data suggest transmission of MERS-CoV among two camel herds in Jordan in 2016 following a single introduction event.
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http://dx.doi.org/10.3390/v13040592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067259PMC
March 2021

High dose of vesicular stomatitis virus-vectored Ebola virus vaccine causes vesicular disease in swine without horizontal transmission.

Emerg Microbes Infect 2021 Dec;10(1):651-663

Department of Diagnostic Medicine/Pathobiology, Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD), College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.

The recent impact of Ebola virus disease (EVD) on public health in Africa clearly demonstrates the need for a safe and efficacious vaccine to control outbreaks and mitigate its threat to global health. ERVEBO® is an effective recombinant Vesicular Stomatitis Virus (VSV)-vectored Ebola virus vaccine (VSV-EBOV) that was approved by the FDA and EMA in late 2019 for use in prevention of EVD. Since the parental virus VSV, which was used to construct VSV-EBOV, is pathogenic for livestock and the vaccine virus may be shed at low levels by vaccinated humans, widespread deployment of the vaccine requires investigation into its infectivity and transmissibility in VSV-susceptible livestock species. We therefore performed a comprehensive clinical analysis of the VSV-EBOV vaccine virus in swine to determine its infectivity and potential for transmission. A high dose of VSV-EBOV resulted in VSV-like clinical signs in swine, with a proportion of pigs developing ulcerative vesicular lesions at the nasal injection site and feet. Uninoculated contact control pigs co-mingled with VSV-EBOV-inoculated pigs did not become infected or display any clinical signs of disease, indicating the vaccine is not readily transmissible to naïve pigs during prolonged close contact. In contrast, virulent wild-type VSV Indiana had a shorter incubation period and was transmitted to contact control pigs. These results indicate that the VSV-EBOV vaccine causes vesicular illness in swine when administered at a high dose. Moreover, the study demonstrates the VSV-EBOV vaccine is not readily transmitted to uninfected pigs, encouraging its safe use as an effective human vaccine.
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http://dx.doi.org/10.1080/22221751.2021.1903343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023602PMC
December 2021

Bat influenza vectored NS1-truncated live vaccine protects pigs against heterologous virus challenge.

Vaccine 2021 Apr 11;39(14):1943-1950. Epub 2021 Mar 11.

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA; Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA; Department of Molecular Microbiology & Immunology, School of Medicine, University of Missouri, Columbia, MO, USA. Electronic address:

Swine influenza is an important disease for the swine industry. Currently used whole inactivated virus (WIV) vaccines can induce vaccine-associated enhanced respiratory disease (VAERD) in pigs when the vaccine strains mismatch with the infected viruses. Live attenuated influenza virus vaccine (LAIV) is effective to protect pigs against homologous and heterologous swine influenza virus infections without inducing VAERD but has safety concerns due to potential reassortment with circulating viruses. Herein, we used a chimeric bat influenza Bat09:mH3mN2 virus, which contains both surface HA and NA gene open reading frames of the A/swine/Texas/4199-2/1998 (H3N2) and six internal genes from the novel bat H17N10 virus, to develop modified live-attenuated viruses (MLVs) as vaccine candidates which cannot reassort with canonical influenza A viruses by co-infection. Two attenuated MLV vaccine candidates including the virus that expresses a truncated NS1 (Bat09:mH3mN2-NS1-128, MLV1) or expresses both a truncated NS1 and the swine IL-18 (Bat09:mH3mN2-NS1-128-IL-18, MLV2) were generated and evaluated in pigs against a heterologous H3N2 virus using the WIV vaccine as a control. Compared to the WIV vaccine, both MLV vaccines were able to reduce lesions and virus replication in lungs and limit nasal virus shedding without VAERD, also induced significantly higher levels of mucosal IgA response in lungs and significantly increased numbers of antigen-specific IFN-γ secreting cells against the challenge virus. However, no significant difference was observed in efficacy between the MLV1 and MLV2. These results indicate that bat influenza vectored MLV vaccines can be used as a safe live vaccine to prevent swine influenza.
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http://dx.doi.org/10.1016/j.vaccine.2021.02.077DOI Listing
April 2021

Experimental re-infected cats do not transmit SARS-CoV-2.

Emerg Microbes Infect 2021 Dec;10(1):638-650

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.

SARS-CoV-2 is the causative agent of COVID-19 and responsible for the current global pandemic. We and others have previously demonstrated that cats are susceptible to SARS-CoV-2 infection and can efficiently transmit the virus to naïve cats. Here, we address whether cats previously exposed to SARS-CoV-2 can be re-infected with SARS-CoV-2. In two independent studies, SARS-CoV-2-infected cats were re-challenged with SARS-CoV-2 at 21 days post primary challenge (DPC) and necropsies performed at 4, 7 and 14 days post-secondary challenge (DP2C). Sentinels were co-mingled with the re-challenged cats at 1 DP2C. Clinical signs were recorded, and nasal, oropharyngeal, and rectal swabs, blood, and serum were collected and tissues examined for histologic lesions. Viral RNA was transiently shed via the nasal, oropharyngeal and rectal cavities of the re-challenged cats. Viral RNA was detected in various tissues of re-challenged cats euthanized at 4 DP2C, mainly in the upper respiratory tract and lymphoid tissues, but less frequently and at lower levels in the lower respiratory tract when compared to primary SARS-CoV-2 challenged cats at 4 DPC. Viral RNA and antigen detected in the respiratory tract of the primary SARS-CoV-2 infected cats at early DPCs were absent in the re-challenged cats. Naïve sentinels co-housed with the re-challenged cats did not shed virus or seroconvert. Together, our results indicate that cats previously infected with SARS-CoV-2 can be experimentally re-infected with SARS-CoV-2; however, the levels of virus shed was insufficient for transmission to co-housed naïve sentinels. We conclude that SARS-CoV-2 infection in cats induces immune responses that provide partial, non-sterilizing immune protection against re-infection.
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http://dx.doi.org/10.1080/22221751.2021.1902753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023599PMC
December 2021

Susceptibility of Midge and Mosquito Vectors to SARS-CoV-2.

J Med Entomol 2021 Mar 4. Epub 2021 Mar 4.

United States Department of Agriculture, Agricultural Research Service, Arthropod-Borne Animal Diseases Research Unit, 1515 College Ave, Manhattan, KS 66502, USA.

SARS-CoV-2 is a recently emerged, highly contagious virus and the cause of the current COVID-19 pandemic. It is a zoonotic virus, although its animal origin is not clear yet. Person-to-person transmission occurs by inhalation of infected droplets and aerosols, or by direct contact with contaminated fomites. Arthropods transmit numerous viral, parasitic, and bacterial diseases; however, the potential role of arthropods in SARS-CoV-2 transmission is not fully understood. Thus far, a few studies have demonstrated that SARS-CoV-2 replication is not supported in cells from certain insect species nor in certain species of mosquitoes after intrathoracic inoculation. In this study, we expanded the work of SARS-CoV-2 susceptibility to biting insects after ingesting a SARS-CoV-2-infected bloodmeal. Species tested included Culicoides sonorensis (Wirth & Jones) (Diptera: Ceratopogonidae) biting midges, as well as Culex tarsalis (Coquillett) and Culex quinquefasciatus (Say) mosquitoes (Diptera: Culicidae), all known biological vectors for numerous RNA viruses. Arthropods were allowed to feed on SARS-CoV-2-spiked blood and at a time point postinfection analyzed for the presence of viral RNA and infectious virus. Additionally, cell lines derived from C. sonorensis (W8a), Aedes aegypti (Linnaeus) (Diptera: Culicidae) (C6/36), Cx. quinquefasciatus (HSU), and Cx. tarsalis (CxTrR2) were tested for SARS-CoV-2 susceptibility. Our results indicate that none of the biting insects, nor the insect cell lines evaluated support SARS-CoV-2 replication, suggesting that these species are unable to be biological vectors of SARS-CoV-2.
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http://dx.doi.org/10.1093/jme/tjab013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989399PMC
March 2021

Environmental Stability of SARS-CoV-2 on Different Types of Surfaces under Indoor and Seasonal Climate Conditions.

Pathogens 2021 Feb 18;10(2). Epub 2021 Feb 18.

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.

Transmission of severe acute respiratory coronavirus 2 (SARS-CoV-2) mainly occurs through direct contact with an infected person via droplets. A potential role of contaminated surfaces in SARS-CoV-2 transmission has been suggested since the virus has been extensively detected on environmental surfaces. These findings have driven the investigation of virus stability on surfaces under several conditions. However, it remains unclear how long the infectious virus survives on surfaces under different climate conditions, which could play a role in predicting the seasonality of SARS-CoV-2. Therefore, the aim of this study was to estimate the virus stability and its biological half-life on various types of surfaces under indoor and seasonal climate conditions. This study revealed that SARS-CoV-2 survived the longest on surfaces under winter conditions, with a survival post-contamination on most surfaces up to 21 days, followed by spring/fall conditions, with a survival up to 7 days. Infectious virus was isolated up to 4 days post-contamination under indoor conditions, whereas no infectious virus was found at 3 days post-contamination under summer conditions. Our study demonstrates the remarkable persistence of SARS-CoV-2 on many different common surfaces, especially under winter conditions, and raises awareness to the potential risk of contaminated surfaces to spread the virus.
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http://dx.doi.org/10.3390/pathogens10020227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922895PMC
February 2021

The N501Y mutation in SARS-CoV-2 spike leads to morbidity in obese and aged mice and is neutralized by convalescent and post-vaccination human sera.

medRxiv 2021 Jan 20. Epub 2021 Jan 20.

The current COVID-19 (coronavirus disease 19) pandemic, caused by SARS-CoV-2, disproportionally affects the elderly and people with comorbidities like obesity and associated type 2 diabetes mellitus. Small animal models are crucial for the successful development and validation of antiviral vaccines, therapies and to study the role that comorbidities have on the outcome of viral infections. The initially available SARS-CoV-2 isolates require adaptation in order to use the mouse angiotensin converting enzyme 2 (mACE-2) entry receptor and to productively infect the cells of the murine respiratory tract. We have "mouse-adapted" SARS-CoV-2 by serial passaging a clinical virus isolate in the lungs of mice. We then used low doses of this virus in mouse models for advanced age, diabetes and obesity. Similar to SARS-CoV-2 infection in humans, the outcome of infection with mouse-adapted SARS-CoV-2 resulted in enhanced morbidity in aged and diabetic obese mice. Mutations associated with mouse adaptation occurred in the S, M, N and ORF8 genes. Interestingly, one mutation in the receptor binding domain of the S protein results in the change of an asparagine to tyrosine residue at position 501 (N501Y). This mutation is also present in the newly emerging SARS-CoV-2 variant viruses reported in the U.K. (20B/501Y.V1, B1.1.7 lineage) that is epidemiologically associated with high human to human transmission. We show that human convalescent and post vaccination sera can neutralize the newly emerging N501Y virus variant with similar efficiency as that of the reference USA-WA1/2020 virus, suggesting that current SARS-CoV-2 vaccines will protect against the 20B/501Y.V1 strain.
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http://dx.doi.org/10.1101/2021.01.19.21249592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836140PMC
January 2021

Myeloid-like γδ T cell subset in the immune response to an experimental Rift Valley fever vaccine in sheep.

Vet Immunol Immunopathol 2021 Mar 8;233:110184. Epub 2021 Jan 8.

Department of Veterinary and Biomedical Sciences, South Dakota State University, 1155 North Campus Drive, Brookings, SD, 57007, USA. Electronic address:

γδ T cells are a numerically significant subset of immune cells in ruminants, where they may comprise up to 70 % of all peripheral blood mononuclear cells (PBMCs) in young animals and 25 % in adults. These cells can be activated through traditional TCR-dependent mechanisms, or alternatively in a TCR-independent manner by pattern recognition receptors and have been shown to uptake antigen, as well as process and present it to αβ T cells. We have identified a novel CD11b+ subset of γδ T cells in normal sheep peripheral blood. An increase in the frequency of these cells in sheep peripheral blood in response to immunization with an experimental recombinant subunit Rift Valley fever (RVF) vaccine was observed. However, injection of the vaccine adjuvant ISA-25VG alone without the recombinant RVF virus antigens demonstrated the same effect, pointing to an antigen-independent innate immune function of CD11b+ γδ T cells in response to the adjuvant. In vitro studies showed repeatable increases of CD11b-, CD14-, CD86-, CD40-, CD72-, and IFNγ- expressing γδ T cells in PBMCs after 24 h of incubation in the absence of a mitogen. Moreover, the majority of these myeloid-like γδ T cells were demonstrated to process exogenous antigen even in the absence of mitogen. ConA activation increased CD25- and MHCII- expression in γδ T cells, but not the myeloid associated receptors CD14 or CD11b or co-stimulatory molecules such as CD86 and CD40. Considering the role of CD11b and CD14 in the activation of innate immunity, we hypothesize that this subpopulation of sheep γδ T cells may function as innate antigen presenting and pro-inflammatory cells during immune responses. The results presented here also suggest that stress molecules and/or damage-associated molecular patterns may be involved in triggering antigen presenting and pro-inflammatory functions of γδ T cells, given their appearance in vitro in the absence of specific stimulation. Taken together, these data suggest that the early appearance of γδ T cells following adjuvant administration and their possible role in early activation of αβ T cell subsets may non-specifically contribute to augmented innate immunity and may promote strong initiation of the adaptive immune response to vaccines in general.
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http://dx.doi.org/10.1016/j.vetimm.2021.110184DOI Listing
March 2021

Topoisomerase 1 inhibition therapy protects against SARS-CoV-2-induced inflammation and death in animal models.

bioRxiv 2020 Dec 1. Epub 2020 Dec 1.

The ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, and analyses, we report that Topoisomerase 1 (Top1) inhibition suppresses lethal inflammation induced by SARS-CoV-2. Therapeutic treatment with two doses of Topotecan (TPT), a FDA-approved Top1 inhibitor, suppresses infection-induced inflammation in hamsters. TPT treatment as late as four days post-infection reduces morbidity and rescues mortality in a transgenic mouse model. These results support the potential of Top1 inhibition as an effective host-directed therapy against severe SARS-CoV-2 infection. TPT and its derivatives are inexpensive clinical-grade inhibitors available in most countries. Clinical trials are needed to evaluate the efficacy of repurposing Top1 inhibitors for COVID-19 in humans.
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http://dx.doi.org/10.1101/2020.12.01.404483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724667PMC
December 2020

Editorial: Emerging Arboviruses.

Front Vet Sci 2020 6;7:593872. Epub 2020 Nov 6.

Department of Diagnostic Medicine/Pathobiology and Center of Excellence for Emerging and Zoonotic Animal Diseases, College of Veterinary Medicine, Kansas State University, Manhattan, KS, United States.

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http://dx.doi.org/10.3389/fvets.2020.593872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677233PMC
November 2020

Middle East Respiratory Syndrome-Coronavirus Seropositive Bactrian Camels, Mongolia.

Vector Borne Zoonotic Dis 2021 02 16;21(2):128-131. Epub 2020 Nov 16.

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, USA.

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.
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http://dx.doi.org/10.1089/vbz.2020.2669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876350PMC
February 2021

A chimeric influenza hemagglutinin delivered by parainfluenza virus 5 vector induces broadly protective immunity against genetically divergent influenza a H1 viruses in swine.

Vet Microbiol 2020 Nov 18;250:108859. Epub 2020 Sep 18.

Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, United States. Electronic address:

Pigs are an important reservoir for human influenza viruses, and influenza causes significant economic loss to the swine industry. As demonstrated during the 2009 H1N1 pandemic, control of swine influenza virus infection is a critical step toward blocking emergence of human influenza virus. An effective vaccine that can induce broadly protective immunity against heterologous influenza virus strains is critically needed. In our previous studies [McCormick et al., 2015; PLoS One, 10(6):e0127649], we used molecular breeding (DNA shuffling) strategies to increase the breadth of the variable and conserved epitopes expressed within a single influenza A virus chimeric hemagglutinin (HA) protein. Chimeric HAs were constructed using parental HAs from the 2009 pandemic virus and swine influenza viruses that had a history of zoonotic transmission to humans. In the current study, we used parainfluenza virus 5 (PIV-5) as a vector to express one of these chimeric HA antigens, HA-113. Recombinant PIV-5 expressing HA-113 (PIV5-113) were rescued, and immunogenicity and protective efficacy were tested in both mouse and pig models. The results showed that PIV5-113 can protect mice and pigs against challenge with viruses expressing parental HAs. The protective immunity was extended against other genetically diversified influenza H1-expressing viruses. Our work demonstrates that PIV5-based influenza vaccines are efficacious as vaccines for pigs. The PIV5 vaccine vector and chimeric HA-113 antigen are discussed in the context of the development of universal influenza vaccines and the potential contribution of PIV5-113 as a candidate universal vaccine.
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http://dx.doi.org/10.1016/j.vetmic.2020.108859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500346PMC
November 2020

SARS-CoV-2 infection, disease and transmission in domestic cats.

Emerg Microbes Infect 2020 Dec;9(1):2322-2332

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of Coronavirus Disease 2019 (COVID-19) and responsible for the current pandemic. Recent SARS-CoV-2 susceptibility studies in cats show that the virus can replicate in these companion animals and transmit to other cats. Here, we present an in-depth study of SARS-CoV-2 infection, disease and transmission in domestic cats. Cats were challenged with SARS-CoV-2 via intranasal and oral routes. One day post challenge (DPC), two sentinel cats were introduced. Animals were monitored for clinical signs, clinicopathological abnormalities and viral shedding. examinations were performed at 4, 7 and 21 DPC. Viral RNA was not detected in blood but transiently in nasal, oropharyngeal and rectal swabs and bronchoalveolar lavage fluid as well as various tissues. Tracheobronchoadenitis of submucosal glands with the presence of viral RNA and antigen was observed in airways of the infected cats. Serology showed that both, principals and sentinels, developed antibodies to SARS-CoV-2. All animals were clinically asymptomatic during the course of the study and capable of transmitting SARS-CoV-2 to sentinels. The results of this study are critical for understanding the clinical course of SARS-CoV-2 in a naturally susceptible host species, and for risk assessment.
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http://dx.doi.org/10.1080/22221751.2020.1833687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594869PMC
December 2020

Susceptibility of swine cells and domestic pigs to SARS-CoV-2.

Emerg Microbes Infect 2020 Dec;9(1):2278-2288

Center of Excellence for Emerging and Zoonotic Animal Diseases, Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.

The emergence of SARS-CoV-2 has resulted in an ongoing global pandemic with significant morbidity, mortality, and economic consequences. The susceptibility of different animal species to SARS-CoV-2 is of concern due to the potential for interspecies transmission, and the requirement for pre-clinical animal models to develop effective countermeasures. In the current study, we determined the ability of SARS-CoV-2 to (i) replicate in porcine cell lines, (ii) establish infection in domestic pigs via experimental oral/intranasal/intratracheal inoculation, and (iii) transmit to co-housed naïve sentinel pigs. SARS-CoV-2 was able to replicate in two different porcine cell lines with cytopathic effects. Interestingly, none of the SARS-CoV-2-inoculated pigs showed evidence of clinical signs, viral replication or SARS-CoV-2-specific antibody responses. Moreover, none of the sentinel pigs displayed markers of SARS-CoV-2 infection. These data indicate that although different porcine cell lines are permissive to SARS-CoV-2, five-week old pigs are not susceptible to infection via oral/intranasal/intratracheal challenge. Pigs are therefore unlikely to be significant carriers of SARS-CoV-2 and are not a suitable pre-clinical animal model to study SARS-CoV-2 pathogenesis or efficacy of respective vaccines or therapeutics.
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http://dx.doi.org/10.1080/22221751.2020.1831405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594707PMC
December 2020

Animal models for COVID-19.

Nature 2020 10 23;586(7830):509-515. Epub 2020 Sep 23.

Department of Immunology, Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (first detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the findings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19.
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http://dx.doi.org/10.1038/s41586-020-2787-6DOI Listing
October 2020

Susceptibility of swine cells and domestic pigs to SARS-CoV-2.

bioRxiv 2020 Aug 16. Epub 2020 Aug 16.

The emergence of SARS-CoV-2 has resulted in an ongoing global pandemic with significant morbidity, mortality, and economic consequences. The susceptibility of different animal species to SARS-CoV-2 is of concern due to the potential for interspecies transmission, and the requirement for pre-clinical animal models to develop effective countermeasures. In the current study, we determined the ability of SARS-CoV-2 to (i) replicate in porcine cell lines, (ii) establish infection in domestic pigs via experimental oral/intranasal/intratracheal inoculation, and (iii) transmit to co-housed naive sentinel pigs. SARS-CoV-2 was able to replicate in two different porcine cell lines with cytopathic effects. Interestingly, none of the SARS-CoV-2-inoculated pigs showed evidence of clinical signs, viral replication or SARS-CoV-2-specific antibody responses. Moreover, none of the sentinel pigs displayed markers of SARS-CoV-2 infection. These data indicate that although different porcine cell lines are permissive to SARS-CoV-2, five-week old pigs are not susceptible to infection via oral/intranasal/intratracheal challenge. Pigs are therefore unlikely to be significant carriers of SARS-CoV-2 and are not a suitable pre-clinical animal model to study SARS-CoV-2 pathogenesis or efficacy of respective vaccines or therapeutics.
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http://dx.doi.org/10.1101/2020.08.15.252395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430576PMC
August 2020

Identification of Newcastle disease virus subgenotype VII.2 in wild birds in Turkey.

BMC Vet Res 2020 Aug 8;16(1):277. Epub 2020 Aug 8.

Department of Virology, Veterinary Faculty, University of Istanbul-Cerrahpasa, Avcilar, Istanbul, Turkey.

Background: Newcastle disease viruses (NDVs) can spread across continents via migratory birds. Hence, we investigated the frequency of NDV in both non-migratory and birds migrating on the Black Sea-Mediterranean flyway, in Istanbul, Turkey. Birds were trapped using nets placed around the Kucukcekmece lake Avcilar, Istanbul, in spring seasons of 2016 and 2018. In total, 297 birds belonging to 42 different species were trapped, categorized according to species and sex, and flocked oropharyngeal swabs were collected. In addition, flocked swabs were also collected from 115 mallards caught by hunters around Edirne and from 207 birds which had been treated in the Veterinary Faculty of Istanbul university-Cerrahpasa. Tissue samples were taken from dead wild birds brought by public to Veterinary Faculty. A total of 619 flocked oropharyngeal swabs were pooled into 206 samples. RNA was extracted from swabs and tissue samples. Real-time RT-PCR prob. assay was used to detect NDV-RNA in samples.

Results: There was no amplification in real time RT-PCR in samples taken from wild birds caught by traps. However, amplification of NDV-F gene was observed in oropharyngeal swabs taken from 2 waterfowls (Common Moorhen and Mallard), and in tissue samples taken from 2 little owls and 1 common kestrel. Sequencing and phylogenetic analyses of these 5 samples for NDV-F gene showed great similarity with NDV subgenotype VII.2 viruses. Analysis also showed that there is a high similarity with the F gene sequences previously reported from Turkey in 2012 and as well as the sequences from neighbouring countries Bulgaria and Georgia and geographically close country such as Pakistan. Although the strains found in this study are closely related, there is a relatively small degree of molecular divergence within 543 bp of F gene of the Turkish NDV isolate and strains detected in Israel, Pakistan, Iran, United Arab Emirates and Belgium.

Conclusions: Our findings revealed the presence of subgenotype VII.2 of NDVs in wild birds in north west of Turkey and demonstrated some degree of molecular evolution when compared to the earlier NDV-VII.2 isolate in Turkey.
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http://dx.doi.org/10.1186/s12917-020-02503-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414739PMC
August 2020

Detection of SARS-CoV-2 by RNAscope in situ hybridization and immunohistochemistry techniques.

Arch Virol 2020 Oct 5;165(10):2373-2377. Epub 2020 Aug 5.

Louisiana Animal Disease Diagnostic Laboratory, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, River Rd, Room 1043, Baton Rouge, LA, 70803, USA.

In situ hybridization (ISH) and immunohistochemistry (IHC) are essential tools to characterize SARS-CoV-2 infection and tropism in naturally and experimentally infected animals and also for diagnostic purposes. Here, we describe three RNAscope-based ISH assays targeting the ORF1ab, spike, and nucleocapsid genes and IHC assays targeting the spike and nucleocapsid proteins of SARS-CoV-2.
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http://dx.doi.org/10.1007/s00705-020-04737-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406679PMC
October 2020

Long amplicon sequencing for improved genetic characterization of African swine fever virus.

J Virol Methods 2020 11 3;285:113946. Epub 2020 Aug 3.

Center of Excellence for Emerging and Zoonotic Animal Diseases, Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA. Electronic address:

African Swine Fever Virus (ASFV) causes a transmissible and fatal disease in pigs that is currently devastating global swine production. Efficient and economical collection of genetic data from ASFV field isolates is essential for bio-surveillance, to limit and control its spread, and to better understand ASF disease ecology. Standard genotyping and subtyping of ASFV field isolates is currently limited to a few variable regions within the ASFV genome. However, more extensive sequencing is necessary to better understand ASFV molecular evolution and identify regions relevant to genetic diversity. In this study, we developed a method for rapid and efficient next generation sequencing of approximately 40% of the ASFV genome using long PCR amplification of six different genomic regions. The amplified regions contain all segments currently used for genotyping and additional genes predicted to contribute to ASFV diversity. The primers used for amplification are broadly compatible with published ASFV genomes, permitting their use on relevant ASFV isolates. This methodology provides the enhanced depth of coverage of amplicon-based sequencing while mitigating complications associated with ASFV whole-genome sequencing. Implementation of this methodology could substantially increase the scale of ASFV genetic data collection, which is necessary to effectively monitor and combat this critical agricultural disease.
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http://dx.doi.org/10.1016/j.jviromet.2020.113946DOI Listing
November 2020

Livestock Challenge Models of Rift Valley Fever for Agricultural Vaccine Testing.

Front Vet Sci 2020 27;7:238. Epub 2020 May 27.

USDA, Arthropod-Borne Animal Diseases Research Unit (ABADRU), Manhattan, KS, United States.

Since the discovery of Rift Valley Fever virus (RVFV) in Kenya in 1930, the virus has become widespread throughout most of Africa and is characterized by sporadic outbreaks. A mosquito-borne pathogen, RVFV is poised to move beyond the African continent and the Middle East and emerge in Europe and Asia. There is a risk that RVFV could also appear in the Americas, similar to the West Nile virus. In light of this potential threat, multiple studies have been undertaken to establish international surveillance programs and diagnostic tools, develop models of transmission dynamics and risk factors for infection, and to develop a variety of vaccines as countermeasures. Furthermore, considerable efforts to establish reliable challenge models of Rift Valley fever virus have been made and platforms for testing potential vaccines and therapeutics in target species have been established. This review emphasizes the progress and insights from a North American perspective to establish challenge models in target livestock such as cattle, sheep, and goats in comparisons to other researchers' reports. A brief summary of the potential role of wildlife, such as buffalo and white-tailed deer as reservoir species will also be discussed.
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http://dx.doi.org/10.3389/fvets.2020.00238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266933PMC
May 2020

African Swine Fever Virus: An Emerging DNA Arbovirus.

Front Vet Sci 2020 13;7:215. Epub 2020 May 13.

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, United States.

African swine fever virus (ASFV) is the sole member of the family , and the only known DNA arbovirus. Since its identification in Kenya in 1921, ASFV has remained endemic in Africa, maintained in a sylvatic cycle between soft ticks and warthogs () which do not develop clinical disease with ASFV infection. However, ASFV causes a devastating and economically significant disease of domestic ( and feral () swine. There is no ASFV vaccine available, and current control measures consist of strict animal quarantine and culling procedures. The virus is highly stable and easily spreads by infected swine, contaminated pork products and fomites, or via transmission by the vector. Competent argasid soft tick vectors are known to exist not only in Africa, but also in parts of Europe and the Americas. Once ASFV is established in the argasid soft tick vector, eradication can be difficult due to the long lifespan of ticks and their proclivity to inhabit the burrows of warthogs or pens and shelters of domestic pigs. Establishment of endemic ASFV infections in wild boar populations further complicates the control of ASF. Between the late 1950s and early 1980s, ASFV emerged in Europe, Russia and South America, but was mostly eradicated by the mid-1990s. In 2007, a highly virulent genotype II ASFV strain emerged in the Caucasus region and subsequently spread into the Russian Federation and Europe, where it has continued to circulate and spread. Most recently, ASFV emerged in China and has now spread to several neighboring countries in Southeast Asia. The high morbidity and mortality associated with ASFV, the lack of an efficacious vaccine, and the complex makeup of the ASFV virion and genome as well as its lifecycle, make this pathogen a serious threat to the global swine industry and national economies. Topics covered by this review include factors important for ASFV infection, replication, maintenance, and transmission, with attention to the role of the argasid tick vector and the sylvatic transmission cycle, current and future control strategies for ASF, and knowledge gaps regarding the virus itself, its vector and host species.
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http://dx.doi.org/10.3389/fvets.2020.00215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237725PMC
May 2020

Investigation of Vector-Borne Viruses in Ticks, Mosquitos, and Ruminants in the Thrace District of Turkey.

Vector Borne Zoonotic Dis 2020 09 12;20(9):670-679. Epub 2020 May 12.

Department of Virology, Veterinary Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.

There is a considerable increase in vector-borne zoonotic diseases around the world, including Turkey, such as Crimean-Congo hemorrhagic fever (CCHF), tick borne encephalitis (TBE), Rift Valley fever (RVF), and West Nile fever (WNF), causing disease and death in humans and animals and significant economical losses. Hence, the aim of this study was to investigate the presence of CCHF virus (CCHFV) and TBE virus (TBEV) in ticks and RVF virus (RVFV) and WNF virus (WNV) in mosquitos, as well as in sheep and cattle, in the Thrace district of the Marmara region, which borders Bulgaria and Greece. Buffy-coat samples from 86 cattle and 81 sheep, as well as 563 ticks and 7390 mosquitos, were collected and examined by quantitative real-time RT-PCR for the presence of CCHFV, TBEV, RVFV, and WNV. All buffy-coat samples from cattle and sheep were negative for these viruses. Similarly, all tick samples were negative for CCHFV-RNA and TBEV-RNA. Among 245 pools representing 7390 mosquitos, only 1 pool sample was found to be positive for WNV-RNA and was confirmed by sequencing. Phylogenetic analysis revealed that it was WNV lineage-2. No RVFV-RNA was detected in the 245 mosquito pools. In conclusion, results of this study indicate that CCHFV, TBEV, and RVFV are not present in livestock and respective vectors in the Thrace district of Marmara region of Turkey, whereas WNV-RNA was found in mosquitos from this region.
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http://dx.doi.org/10.1089/vbz.2019.2532DOI Listing
September 2020

A Critical Needs Assessment for Research in Companion Animals and Livestock Following the Pandemic of COVID-19 in Humans.

Vector Borne Zoonotic Dis 2020 06 5;20(6):393-405. Epub 2020 May 5.

Veterinary Pathobiology, Purdue University, West Lafayette, Indiana, USA.

The emergence of novel coronavirus (SARS-CoV-2) in Wuhan, China, in November 2019 and a growing body of information compel inquiry regarding the transmissibility of infection between humans and certain animal species. Although there are a number of issues to be considered, the following points are most urgent: The potential for domesticated (companion) animals to serve as a reservoir of infection contributing to continued human-to-human disease, infectivity, and community spread. The ramifications to food security, economy, and trade issues should coronavirus establish itself within livestock and poultry. The disruption to national security if SARS-CoV-2 and its fairly well-established effects on smell (hyposmia/anosmia) to critical military service animals including explosive detector dog, narcotics detector dog, specialized search dog, combat tracker dog, mine detection dog, tactical explosive detector dog, improvised explosive device detector dog, patrol explosive detector dog, and patrol narcotics detector dog, as well as multipurpose canines used by special operations such as used by the U.S. customs and border protection agency (, Beagle Brigade). This article presents in chronological order data that both individually (as received independently from multiple countries) and collectively urge studies that elucidate the following questions. 1.What animal species can be infected with SARS-CoV-2, the likely sources of infection, the period of infectivity, and transmissibility between these animals and to other animal species and humans? 2.What are the best diagnostic tests currently available for companion animals and livestock? 3.What expressions of illness in companion and other animal species can serve as disease markers? Although it is recognized that robust funding and methodology need to be identified to apply the best scientific investigation into these issues, there may be easily identifiable opportunities to capture information that can guide decision and study. First, it may be possible to quickly initiate a data collection strategy using in-place animal gatekeepers, such as zookeepers, veterinarians, kennel owners, feed lots, and military animal handlers. If provided a simple surveillance form, their detection of symptoms (lethargy, hyposmia, anosmia, and others) might be quickly reported to a central data collection site if one were created. Second, although current human COVID-19 disease is aligning around areas of population density and cluster events, it might be possible to overlay animal species density or veterinary reports that could signal some disease association in animals with COVID-19 patients. Unfortunately, although companion animals and zoo species have repeatedly served as sentinels for emerging infectious diseases, they do not currently fall under the jurisdiction of any federal agency and are not under surveillance.
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http://dx.doi.org/10.1089/vbz.2020.2650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249469PMC
June 2020

First report of influenza D virus infection in Turkish cattle with respiratory disease.

Res Vet Sci 2020 Jun 21;130:98-102. Epub 2020 Feb 21.

IHAP, Université de Toulouse, INRA, ENVT, 23 Chemin des Capelles, 31076 Toulouse, France.

Bovine respiratory infections are the most economically important diseases affecting the cattle industry worldwide including Turkey. Influenza D virus (IDV) could play an important role to trigger bovine respiratory disease (BRD) complex. Since, there is no data about the presence and genotypes of IDV in Turkish cattle herds; this study was performed to investigate IDV in cattle in Turkey. Animals analyzed in this study were from commercial cattle farms having respiratory disease in calves with significant mortality. Nasal swabs and tissue samples from cattle in Marmara, Inner Anatolia and Aegean region of Turkey were analyzed by real-time RT-PCR assay to detect IDV. Among 76 samples form 12 cattle herds, IDV was detected in 3 cattle in a herd. Sequencing and phylogenetic analysis of partial hemagglutinin esterase fusion (HEF) gene showed that the Turkish strain is 95% identical to its European and US counterparts, which suggest intercontinental spread of the virus. These findings highlight the need for future continuous surveillance on larger scale to determine the distribution pattern and evolution of this novel emerging pathogen in Turkish cattle industry.
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http://dx.doi.org/10.1016/j.rvsc.2020.02.017DOI Listing
June 2020

Novel Reassortant Avian Influenza A(H9N2) Virus Isolate in Migratory Waterfowl in Hubei Province, China.

Front Microbiol 2020 13;11:220. Epub 2020 Feb 13.

College of Wildlife and Protected Area, Northeast Forestry University, Harbin, China.

In December 2017, an influenza A(H9N2) virus (B51) was isolated from migratory waterfowl in Hubei Province, China. Phylogenetic analysis demonstrated that B51 is a novel reassortant influenza virus containing segments from human H7N4 virus and North American wild bird influenza viruses. This suggest that B51 has undergone multiple reassortment events.
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http://dx.doi.org/10.3389/fmicb.2020.00220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031422PMC
February 2020

Evaluation of A Baculovirus-Expressed VP2 Subunit Vaccine for the Protection of White-Tailed Deer () from Epizootic Hemorrhagic Disease.

Vaccines (Basel) 2020 Jan 31;8(1). Epub 2020 Jan 31.

Center of Excellence for Emerging and Zoonotic Animal Diseases, and the Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.

Epizootic hemorrhagic disease virus (EHDV) is an arthropod-transmitted RNA virus and the causative agent of epizootic hemorrhagic disease (EHD) in wild and domestic ruminants. In North America, white-tailed deer (WTD) experience the highest EHD-related morbidity and mortality, although clinical disease is reported in cattle during severe epizootics. No commercially licensed EHDV vaccine is available in North America. The objective of this study was to develop and evaluate a subunit vaccine candidate to control EHD in WTD. Recombinant VP2 (rVP2) outer capsid proteins of EHDV serotypes 2 (EHDV-2) and 6 (EHDV-6) were produced in a baculovirus-expression system. Mice and cattle vaccinated with EHDV-2 or EHDV-6 rVP2 produced homologous virus-neutralizing antibodies. In an immunogenicity/efficacy study, captive-bred WTD received 2 doses of EHDV-2 rVP2 or sham vaccine, then were challenged with wild-type EHDV-2 at 30 d post vaccination. None of the rVP2-vaccinated deer developed clinical disease, no viral RNA was detected in their blood or tissues (liver, lung, spleen, kidney), and no EHDV-induced lesions were observed. Sham-vaccinated deer developed clinical disease with viremia and typical EHD vascular lesions. Here, we demonstrate a rVP2 subunit vaccine that can provide protective immunity from EHDV infection and which may serve as an effective tool in preventing clinical EHD and reducing virus transmission.
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http://dx.doi.org/10.3390/vaccines8010059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157196PMC
January 2020