Evolutionary Insights into IL17A in Lagomorphs

In leporids, IL17A had been implicated in the host defense against extracellular pathogens, such asFrancisella tularensisthat infects hares and rabbits and causes the zoonotic disease tularemia. Here, we studied IL17A from five lagomorphs, European rabbit, pygmy rabbit, brush rabbit, European brown hare, and American pika. We observed that this protein is highly conserved between these species, with a similarity of 97–99% in leporids and ~88% between leporids and American pika. The exon/intron structure, N-glycosylation sites, and cysteine residues are conserved between lagomorphs. However, at codon 88, one of the interaction sites between IL17A and its receptor IL17RA, there is an Arg>Pro mutation that only occurs in European rabbit and European brown hare. This could induce critical alterations in the IL17A structure and conformation and consequently modify its function. The differences observed between leporids and humans or rodents might also represent important alterations in protein structure and function. In addition, as for other interleukins, IL17A sequences of human and European rabbit are more closely related than the sequences of human and mouse or European rabbit and mouse. This study gives further support to the hypothesis that European rabbit might be a more suitable animal model for studies on human IL17.

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Viral Disease in Lagomorphs: A Molecular Perspective

10.5772/intechopen.98272 ◽

2021 ◽

Author(s):

Kevin P. Dalton ◽

Ana Podadera ◽

José Manuel Martin Alonso ◽

Inés Calonge Sanz ◽

Ángel Luis Álvarez Rodríguez ◽

...

Keyword(s):

Viral Disease ◽

Myxoma Virus ◽

Lepus Europaeus ◽

European Rabbit ◽

Great Effort ◽

Brown Hare ◽

European Brown Hare ◽

European Brown Hare Syndrome ◽

Molecular Aspects ◽

Species Specific

Our understanding of molecular biology of the viruses that infect lagomorphs is largely limited to the leporipoxvirus myxoma virus (MYXV) and the lagoviruses rabbit haemorrhagic disease virus (RHDV) and European brown hare syndrome virus (EBHSV) that infect the European rabbit (Oryctolagus cuniculus) and the European brown hare (Lepus europaeus) respectively. Thanks to the great effort of historic surveillance studies and careful sample archiving, the molecular evolution of these viruses is being resolved. Although historically considered viruses that cause species specific diseases recent reports show that several lagomorphs may now face the threat of these maladies. The driving factors behind these changes has not been determined and the effect of these species jumps on lagomorph populations has yet to be seen. Lagomorphs are also affected by several other lesser studied viral diseases. In addition, recent metagenomic studies have led to the identification of novel lagomorph viruses the importance of these to lagomorph health remains to be fully determined. In this chapter we summarize molecular aspects of viruses that infect lagomorphs, paying particular attention to recent interspecies infections.

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Evolutionary history of an MHC gene in two leporid species: characterisation of Mhc-DQA in the European brown hare and comparison with the European rabbit

Immunogenetics ◽

10.1007/s00251-008-0349-4 ◽

2008 ◽

Vol 61 (2) ◽

pp. 131-144 ◽

Cited By ~ 26

Author(s):

Joëlle Goüy de Bellocq ◽

Franz Suchentrunk ◽

Stuart J. E. Baird ◽

Helmut Schaschl

Keyword(s):

Evolutionary History ◽

European Rabbit ◽

Brown Hare ◽

European Brown Hare ◽

History Of

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Infectious Diseases in European Brown Hare (lepus europaeus)

Wildlife Biology in Practice ◽

10.2461/wbp.2005.1.11 ◽

2005 ◽

Vol 1 (1) ◽

Cited By ~ 15

Author(s):

G. Wibbelt ◽

K. FrÃ¶lich

Keyword(s):

Infectious Diseases ◽

Lepus Europaeus ◽

Brown Hare ◽

European Brown Hare

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A Mucin-Specific Protease Enables Molecular and Functional Analysis of Human Cancer-Associated Mucins

10.26434/chemrxiv.7330676 ◽

2018 ◽

Author(s):

Stacy A. Malaker ◽

Kayvon Pedram ◽

Michael J. Ferracane ◽

Elliot C. Woods ◽

Jessica Kramer ◽

...

Keyword(s):

Mass Spectrometry ◽

Molecular Mechanisms ◽

Cultured Cells ◽

High Resolution Mass Spectrometry ◽

Human Cancer ◽

Glycosylation Sites ◽

Bacterial Protease ◽

Specific Protease ◽

To Come ◽

And Function

<div> <div> <div> <p>Mucins are a class of highly O-glycosylated proteins that are ubiquitously expressed on cellular surfaces and are important for human health, especially in the context of carcinomas. However, the molecular mechanisms by which aberrant mucin structures lead to tumor progression and immune evasion have been slow to come to light, in part because methods for selective mucin degradation are lacking. Here we employ high resolution mass spectrometry, polymer synthesis, and computational peptide docking to demonstrate that a bacterial protease, called StcE, cleaves mucin domains by recognizing a discrete peptide-, glycan-, and secondary structure- based motif. We exploited StcE’s unique properties to map glycosylation sites and structures of purified and recombinant human mucins by mass spectrometry. As well, we found that StcE will digest cancer-associated mucins from cultured cells and from ovarian cancer patient-derived ascites fluid. Finally, using StcE we discovered that Siglec-7, a glyco-immune checkpoint receptor, specifically binds sialomucins as biological ligands, whereas the related Siglec-9 receptor does not. Mucin-specific proteolysis, as exemplified by StcE, is therefore a powerful tool for the study of glycoprotein structure and function and for deorphanizing mucin-binding receptors. </p> </div> </div> </div>

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A preliminary study on the detection of potential contaminants in the European brown hare (Lepus europaeus) by suspect and microplastics screening

Environmental Advances ◽

10.1016/j.envadv.2021.100045 ◽

2021 ◽

Vol 4 ◽

pp. 100045

Author(s):

Romana Hornek-Gausterer ◽

Herbert Oberacher ◽

Vera Reinstadler ◽

Christina Hartmann ◽

Bettina Liebmann ◽

...

Keyword(s):

Lepus Europaeus ◽

Brown Hare ◽

European Brown Hare ◽

Preliminary Study

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Confirmation of myxomatosis in a European brown hare in Great Britain: Myxomatosis

Veterinary Record ◽

10.1136/vr.g4621 ◽

2014 ◽

Vol 175 (3) ◽

pp. 75-76 ◽

Cited By ~ 14

Author(s):

A. Barlow ◽

K. Lawrence ◽

D. Everest ◽

A. Dastjerdi ◽

C. Finnegan ◽

...

Keyword(s):

Great Britain ◽

Brown Hare ◽

European Brown Hare

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Functional Role of N-Linked Glycosylation in Pseudorabies Virus Glycoprotein gH

Journal of Virology ◽

10.1128/jvi.00084-18 ◽

2018 ◽

Vol 92 (9) ◽

pp. e00084-18 ◽

Cited By ~ 3

Author(s):

Melina Vallbracht ◽

Sascha Rehwaldt ◽

Barbara G. Klupp ◽

Thomas C. Mettenleiter ◽

Walter Fuchs

Keyword(s):

Pseudorabies Virus ◽

Viral Envelope ◽

Fusion Activity ◽

Virus Particles ◽

Glycosylation Sites ◽

Functional Relevance ◽

And Function ◽

Cell Spread

ABSTRACTMany viral envelope proteins are modified by asparagine (N)-linked glycosylation, which can influence their structure, physicochemical properties, intracellular transport, and function. Here, we systematically analyzed the functional relevance of N-linked glycans in the alphaherpesvirus pseudorabies virus (PrV) glycoprotein H (gH), which is an essential component of the conserved core herpesvirus fusion machinery. Upon gD-mediated receptor binding, the heterodimeric complex of gH and gL activates gB to mediate fusion of the viral envelope with the host cell membrane for viral entry. gH contains five potential N-linked glycosylation sites at positions 77, 162, 542, 604, and 627, which were inactivated by conservative mutations (asparagine to glutamine) singly or in combination. The mutated proteins were tested for correct expression and fusion activity. Additionally, the mutated gH genes were inserted into the PrV genome for analysis of function during virus infection. Our results demonstrate that all five sites are glycosylated. Inactivation of the PrV-specific N77 or the conserved N627 resulted in significantly reducedin vitrofusion activity, delayed penetration kinetics, and smaller virus plaques. Moreover, substitution of N627 greatly affected transport of gH in transfected cells, resulting in endoplasmic reticulum (ER) retention and reduced surface expression. In contrast, mutation of N604, which is conserved in theVaricellovirusgenus, resulted in enhancedin vitrofusion activity and viral cell-to-cell spread. These results demonstrate a role of the N-glycans in proper localization and function of PrV gH. However, even simultaneous inactivation of all five N-glycosylation sites of gH did not severely inhibit formation of infectious virus particles.IMPORTANCEHerpesvirus infection requires fusion of the viral envelope with cellular membranes, which involves the conserved fusion machinery consisting of gB and the heterodimeric gH/gL complex. The bona fide fusion protein gB depends on the presence of the gH/gL complex for activation. Viral envelope glycoproteins, such as gH, usually contain N-glycans, which can have a strong impact on their folding, transport, and functions. Here, we systematically analyzed the functional relevance of all five predicted N-linked glycosylation sites in the alphaherpesvirus pseudorabies virus (PrV) gH. Despite the fact that mutation of specific sites affected gH transport,in vitrofusion activity, and cell-to-cell spread and resulted in delayed penetration kinetics, even simultaneous inactivation of all five N-glycosylation sites of gH did not severely inhibit formation of infectious virus particles. Thus, our results demonstrate a modulatory but nonessential role of N-glycans for gH function.

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