Tissue Microarrays to Visualize Influenza D Attachment to Host Receptors in the Respiratory Tract of Farm Animals

The trimeric hemagglutinin-esterase fusion protein (HEF) of influenza D virus (IDV) binds 9-O-acetylated sialic acid receptors, which are expressed in various host species. While cattle are the main reservoir for IDV, the viral genome has also been detected in domestic pigs. In addition, antibodies against IDV have been detected in other farm animals such as sheep, goats, and horses, and even in farmers working with IDV positive animals. Viruses belonging to various IDV clades circulate, but little is known about their differences in host and tissue tropism. Here we used recombinantly produced HEF proteins (HEF S57A) from the major clades D/Oklahoma (D/OK) and D/Oklahoma/660 (D/660) to study their host and tissue tropism and receptor interactions. To this end, we developed tissue microarrays (TMA) composed of respiratory tissues from various farm animals including cattle, domestic pigs, sheep, goats, and horses. Protein histochemical staining of farm animal respiratory tissue-microarrays with HEF proteins showed that cattle have receptors present over the entire respiratory tract while receptors are only present in the nasal and pharyngeal epithelium of pigs, sheep, goats, and horses. No differences in tropism for tissues and animals were observed between clades, while hemagglutination assays showed that D/OK has a 2-fold higher binding affinity than D/660 for receptors on red blood cells. The removal of O-acetylation from receptors via saponification treatment confirmed that receptor-binding of both clades was dependent on O-acetylated sialic acids.

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Enterovirus D: A Small but Versatile Species

Microorganisms ◽

10.3390/microorganisms9081758 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1758

Author(s):

Ines Cordeiro Filipe ◽

Mariana Soares Guedes ◽

Evgeny M. Zdobnov ◽

Caroline Tapparel

Keyword(s):

Nervous System ◽

Gastrointestinal Tract ◽

Infectious Diseases ◽

Respiratory Tract ◽

Genome Organization ◽

Neurological Complications ◽

Tissue Tropism ◽

Functional Elements ◽

Diverse Range ◽

Causative Agents

Enteroviruses (EVs) from the D species are the causative agents of a diverse range of infectious diseases in spite of comprising only five known members. This small clade has a diverse host range and tissue tropism. It contains types infecting non-human primates and/or humans, and for the latter, they preferentially infect the eye, respiratory tract, gastrointestinal tract, and nervous system. Although several Enterovirus D members, in particular EV-D68, have been associated with neurological complications, including acute myelitis, there is currently no effective treatment or vaccine against any of them. This review highlights the peculiarities of this viral species, focusing on genome organization, functional elements, receptor usage, and pathogenesis.

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Lower Respiratory Tract Infection Therapy – the Role of Ciprofloxacin

Journal of International Medical Research ◽

10.1177/030006059502300501 ◽

1995 ◽

Vol 23 (5) ◽

pp. 315-327 ◽

Cited By ~ 22

Author(s):

A P Ball ◽

G S Tillotson

Keyword(s):

Respiratory Tract ◽

Moraxella Catarrhalis ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Lower Respiratory Tract Infections ◽

Tissue Penetration ◽

Tract Infections ◽

Respiratory Tissue ◽

Unpublished Information

Lower respiratory tract infections account for a large proportion of prescribed antibiotics and, with emerging resistance to standard agents, the introduction of the fluoroquinolones, in particular ciprofloxacin, has provided a further component in the armamentarium. This review encompasses 37 published clinical trials which featured ciprofloxacin; 3274 patients with lower respiratory tract infections were treated with this agent; in 94.1% of patients treatment was clinically successful and 90.9% of cases showed eradication of the causative pathogen. When these data were supplemented with previously unpublished Information from the clinical trial database, specific organism eradication rates of 86.1%, 96.2% and 94.6% for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, respectively, were observed. These findings suggest that the high respiratory tissue penetration of ciprofloxacin and the achievable minimum inhibitory concentrations lead to acceptable clinical outcomes in lower respiratory tract infections.

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A note on pigs’ knowledge of hidden objects

Archives Animal Breeding ◽

10.7482/0003-9438-56-086 ◽

2013 ◽

Vol 56 (1) ◽

pp. 861-872 ◽

Cited By ~ 5

Author(s):

C. Nawroth ◽

M. Ebersbach ◽

E. von Borell

Keyword(s):

Sus Scrofa ◽

Object Permanence ◽

Farm Animals ◽

Food Sources ◽

Abstract Object ◽

Test Setup ◽

Domestic Pigs ◽

Study Designs ◽

Free Ranging ◽

Sus Scrofa Domestica

Abstract. Object permanence is the notion that objects continue to exist even when they are out of observer´s sight. This ability is adaptive not only for free ranging animals who have to cope with a dangerous and highly changeable environment, allowing them to be aware of predators sneaking in their proximity or to keep track of conspecifics or food sources, even when out of sight. Farm animals, too, might profit from object permanence as the ability to follow the trajectory of hidden food or objects may lead to a higher predictability of subjects' environment, which in turn might affect the level of stress under husbandry conditions. We conducted two experiments to examine the ability of object permanence in young domestic pigs (Sus scrofa domestica). For this purpose we used a test setup that was formerly developed for primates and adopted it to the behavioural constraints of pigs. A rewarded object was hidden in one of three hiding locations with an increasing complexity of the objects movement through successive test sessions. Subjects were confronted with visible and invisible displacement tasks as well as with transpositions of hidden objects in different contextual settings. Pigs solved visible, but not invisible displacements or transpositions, indicating that they have difficulties to keep track of once hidden and then moved objects. This should be taken into account when designing husbandry environments or study designs.

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Python nidoviruses, more than respiratory pathogens

10.1101/2020.04.10.036640 ◽

2020 ◽

Author(s):

Eva Dervas ◽

Jussi Hepojoki ◽

Teemu Smura ◽

Barbara Prähauser ◽

Katharina Windbichler ◽

...

Keyword(s):

Respiratory Tract ◽

Broad Spectrum ◽

Target Cells ◽

Tissue Tropism ◽

High Morbidity ◽

Renal Tubules ◽

Rt Pcr ◽

Organ Systems ◽

Systemic Spread ◽

Human Viruses

ABSTRACTIn recent years nidoviruses have emerged as an important respiratory pathogen of reptiles, affecting especially captive python populations. In pythons, nidovirus infection induces an inflammation of the upper respiratory and alimentary tract which can develop into a severe and often fatal proliferative pneumonia. We observed pyogranulomatous and fibrinonecrotic lesions in organ systems other than the respiratory tract during full post mortem examinations on 30 nidovirus RT-PCR positive pythons of varying species originating from Switzerland and Spain. The observations prompted us to study whether the atypical tissue tropism associates with previously unknown nidoviruses or changes in the nidovirus genome. RT-PCR and inoculation of Morelia viridis cell cultures served to recruit the cases and to obtain virus isolates. Immunohistochemistry and immunofluorescence staining against nidovirus nucleoprotein demonstrated that the virus not only infects a broad spectrum of epithelial (respiratory and alimentary epithelium, hepatocytes, renal tubules, pancreatic ducts etc.), but also intravascular monocytes, intralesional macrophages and endothelial cells. By next-generation sequencing we obtained full length genome for a novel nidovirus species circulating in Switzerland. Analysis of viral genomes recovered from pythons showing nidovirus infection-associated respiratory or systemic disease did not explain the observed phenotypes. The results indicate that python nidoviruses have a broad cell and tissue tropism, further suggesting that the course of infection could vary and involve lesions in a broad spectrum of tissues and organ systems as a consequence of monocyte-mediated systemic spread of the virus.IMPORTANCEDuring the last years, python nidoviruses have become a primary cause of fatal disease in pythons. Nidoviruses represent a threat to captive snake collections, as they spread rapidly and can be associated with high morbidity and mortality. Our study indicates that, different from previously evidence, the viruses do not only affect the respiratory tract, but can spread in the entire body with blood monocytes, have a broad spectrum of target cells, and can induce a variety of lesions. Nidovirales is an order of animal and human viruses that compromise important zoonotic pathogens such as MERS-CoV and SARS-CoV, as well as the recently emerged SARS-CoV-2. Python nidoviruses belong to the same subfamily as the mentioned human viruses and show similar characteristics (rapid spread, respiratory and gastrointestinal tropism, etc.). The present study confirms the relevance of natural animal diseases to better understand the complexity of viruses of the order nidovirales.

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Bacteria-induced expression of the pig-derived protegrin-1 transgene specifically in the respiratory tract of mice enhances resistance to airway bacterial infection

Scientific Reports ◽

10.1038/s41598-020-73084-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Fang Zeng ◽

Chengcheng Zhao ◽

Xiao Wu ◽

Rui Dong ◽

Guoling Li ◽

...

Keyword(s):

Transgenic Mice ◽

Respiratory Tract ◽

Bacterial Infection ◽

Bacterial Infections ◽

Bacterial Resistance ◽

Rapid Development ◽

Bacterial Load ◽

Animal Production ◽

Farm Animal ◽

Farm Animals

Abstract About 70% of all antibiotics produced in the world are used in the farm animal industry. The massive usage of antibiotics during farm animal production has caused rapid development of antibiotic resistance in bacteria, which poses a serious risk to human and livestock health when treating bacterial infections. Protegrin-1 (PG-1) is a potent antimicrobial peptide (AMP). It was initially identified in pig leukocytes with a broad-spectrum antibacterial and antiviral activity, and a low rate of inducing bacterial resistance. To develop a genetic approach for reducing the use of antibiotics in farm animal production, we produced transgenic mice carrying a bovine tracheal AMP gene promoter-controlled PG-1 transgene. The PG-1 transgene was specifically expressed in the respiratory tract of transgenic mice upon induction by bacterial infection. These PG-1 transgenic mice exhibited enhanced resistance to nasal bacterial infection as the transgenic mice showed a higher survival rate (79.17% VS. 34.78%), lower bacterial load and milder histological severity than their wild-type control littermates. The improved resistance to bacterial infection in the PG-1 transgenic mice could be resulted from the direct bacteria-killing activities of PG-1, and the immunomodulatory effects of PG-1 via stimulating interleukin 1 beta secretion. The present study provides a promising genetic strategy to prevent airway bacterial infections in farm animals by bacteria-inducible tissue-specific expression of PG-1 transgene. This approach may also be helpful for decreasing the possibility of inducing bacterial resistance during farm animal production.

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Detection of Bordetella avium by TaqMan real-time PCR in tracheal swabs from wildlife birds

Polish Journal of Veterinary Sciences ◽

10.1515/pjvs-2017-0005 ◽

2017 ◽

Vol 20 (1) ◽

pp. 31-36 ◽

Cited By ~ 2

Author(s):

T. Stenzel ◽

D. Pestka ◽

B. Tykałowski ◽

M. Śmiałek ◽

A. Koncicki ◽

...

Keyword(s):

Respiratory Tract ◽

Real Time ◽

Real Time Pcr ◽

Genetic Material ◽

Positive Control ◽

Farm Animals ◽

Diagnostic Laboratory ◽

Bacterial Dna ◽

Bordetella Avium ◽

Low Prevalence

Abstract Bordetella avium, the causing agent of bordetellosis, a highly contagious infection of the respiratory tract in young poultry, causes significant losses in poultry farming throughout the world. Wildlife birds can be a reservoir of various pathogens that infect farm animals. For this reason the studies were conducted to estimate the prevalence of Bordetella avium in wildlife birds in Poland. Tracheal swab samples were collected from 650 birds representing 27 species. The bacterial DNA was isolated directly from the swabs and screened for Bordetella avium by TaqMan real-time PCR. The assay specificity was evaluated by testing DNA isolated from 8 other bacteria that can be present in avian respiratory tract, and there was no amplification from non-Bordetella avium agents. Test sensitivity was determined by preparing standard tenfold serial dilutions of DNA isolated from positive control. The assay revealed to be sensitive, with detection limit of approximately 4.07x10^2 copies of Bordetella avium DNA. The genetic material of Bordetella avium was found in 54.54% of common pheasants, in 9.09% of Eurasian coots, in 3.22% of black-headed gulls and in 2.77% of mallard ducks. The results of this study point to low prevalence of Bordetella avium infections in wildlife birds. The results also show that described molecular assay proved to be suitable for the rapid diagnosis of bordetellosis in the routine diagnostic laboratory.

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Tissue Tropism of Swine Influenza Viruses and Reassortants in Ex Vivo Cultures of the Human Respiratory Tract and Conjunctiva

Journal of Virology ◽

10.1128/jvi.05662-11 ◽

2011 ◽

Vol 85 (22) ◽

pp. 11581-11587 ◽

Cited By ~ 20

Author(s):

R. W. Y. Chan ◽

S. S. R. Kang ◽

H.-L. Yen ◽

A. C. L. Li ◽

L. L. S. Tang ◽

...

Keyword(s):

Respiratory Tract ◽

Ex Vivo ◽

Swine Influenza ◽

Influenza Viruses ◽

Tissue Tropism ◽

Human Respiratory Tract

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The Remarkable Evolutionary Plasticity of Coronaviruses by Mutation and Recombination: Insights for the COVID-19 Pandemic and the Future Evolutionary Paths of SARS-CoV-2

Viruses ◽

10.3390/v14010078 ◽

2022 ◽

Vol 14 (1) ◽

pp. 78

Author(s):

Grigorios D. Amoutzias ◽

Marios Nikolaidis ◽

Eleni Tryfonopoulou ◽

Katerina Chlichlia ◽

Panayotis Markoulatos ◽

...

Keyword(s):

Point Mutations ◽

Host Tissue ◽

Farm Animals ◽

Tissue Tropism ◽

Molecular Processes ◽

Positive Sense ◽

The Future ◽

Evolutionary Context ◽

Evolutionary Paths ◽

The Impact

Coronaviruses (CoVs) constitute a large and diverse subfamily of positive-sense single-stranded RNA viruses. They are found in many mammals and birds and have great importance for the health of humans and farm animals. The current SARS-CoV-2 pandemic, as well as many previous epidemics in humans that were of zoonotic origin, highlights the importance of studying the evolution of the entire CoV subfamily in order to understand how novel strains emerge and which molecular processes affect their adaptation, transmissibility, host/tissue tropism, and patho non-homologous genicity. In this review, we focus on studies over the last two years that reveal the impact of point mutations, insertions/deletions, and intratypic/intertypic homologous and non-homologous recombination events on the evolution of CoVs. We discuss whether the next generations of CoV vaccines should be directed against other CoV proteins in addition to or instead of spike. Based on the observed patterns of molecular evolution for the entire subfamily, we discuss five scenarios for the future evolutionary path of SARS-CoV-2 and the COVID-19 pandemic. Finally, within this evolutionary context, we discuss the recently emerged Omicron (B.1.1.529) VoC.

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Epidemiology of bacteria and viruses in the respiratory tract of humans and domestic pigs

Apmis ◽

10.1111/apm.13046 ◽

2020 ◽

Vol 128 (6) ◽

pp. 451-462

Author(s):

Jennifer Bunke ◽

Kerstin Receveur ◽

Ann Christin Oeser ◽

Imke Gutsmann ◽

Sabine Schubert ◽

...

Keyword(s):

Respiratory Tract ◽

Domestic Pigs

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Comparison of Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Binding to ACE2 Receptors from Human, Pets, Farm Animals, and Putative Intermediate Hosts

Journal of Virology ◽

10.1128/jvi.00831-20 ◽

2020 ◽

Vol 94 (15) ◽

Cited By ~ 33

Author(s):

Xiaofeng Zhai ◽

Jiumeng Sun ◽

Ziqing Yan ◽

Jie Zhang ◽

Jin Zhao ◽

...

Keyword(s):

Amino Acids ◽

Severe Acute Respiratory Syndrome ◽

Respiratory Tract ◽

Binding Site ◽

Protein S ◽

Spike Protein ◽

Farm Animals ◽

Intermediate Hosts ◽

Species Barrier ◽

Interaction Sites

ABSTRACT The emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in a pandemic. Here, we used X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2. Comparing the interaction sites of ACE2 proteins known to serve or not serve as receptors allows the definition of residues important for binding. From the 20 amino acids in ACE2 that contact S, up to 7 can be replaced and ACE2 can still function as the SARS-CoV-2 receptor. These variable amino acids are clustered at certain positions, mostly at the periphery of the binding site, while changes of the invariable residues prevent S binding or infection of the respective animal. Some ACE2 proteins even tolerate the loss or acquisition of N-glycosylation sites located near the S interface. Of note, pigs and dogs, which are not infected or are not effectively infected and have only a few changes in the binding site, exhibit relatively low levels of ACE2 in the respiratory tract. Comparison of the RBD of S of SARS-CoV-2 with that from bat coronavirus strain RaTG13 (Bat-CoV-RaTG13) and pangolin coronavirus (Pangolin-CoV) strain hCoV-19/pangolin/Guangdong/1/2019 revealed that the latter contains only one substitution, whereas Bat-CoV-RaTG13 exhibits five. However, ACE2 of pangolin exhibits seven changes relative to human ACE2, and a similar number of substitutions is present in ACE2 of bats, raccoon dogs, and civets, suggesting that SARS-CoV-2 may not be especially adapted to ACE2 of any of its putative intermediate hosts. These analyses provide new insight into the receptor usage and animal source/origin of SARS-CoV-2. IMPORTANCE SARS-CoV-2 is threatening people worldwide, and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear, and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes, indicating that the species barrier might be low. Exceptions are dogs and especially pigs, which revealed relatively low ACE2 expression levels in the respiratory tract. Monitoring of animals is necessary to prevent the generation of a new coronavirus reservoir. Finally, our analysis also showed that SARS-CoV-2 may not be specifically adapted to any of its putative intermediate hosts.

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