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      The Pathogenesis and Immune Evasive Mechanisms of Equine Herpesvirus Type 1

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          Abstract

          Equine herpesvirus type 1 (EHV-1) is an alphaherpesvirus related to pseudorabies virus (PRV) and varicella-zoster virus (VZV). This virus is one of the major pathogens affecting horses worldwide. EHV-1 is responsible for respiratory disorders, abortion, neonatal foal death and equine herpes myeloencephalopathy (EHM). Over the last decade, EHV-1 has received growing attention due to the frequent outbreaks of abortions and/or EHM causing serious economical losses to the horse industry worldwide. To date, there are no effective antiviral drugs and current vaccines do not provide full protection against EHV-1-associated diseases. Therefore, there is an urgent need to gain a better understanding of the pathogenesis of EHV-1 in order to develop effective therapies. The main objective of this review is to provide state-of-the-art information on the pathogenesis of EHV-1. We also highlight recent findings on EHV-1 immune evasive strategies at the level of the upper respiratory tract, blood circulation and endothelium of target organs allowing the virus to disseminate undetected in the host. Finally, we discuss novel approaches for drug development based on our current knowledge of the pathogenesis of EHV-1.

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          Most cited references119

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          Allergenic pollen and pollen allergy in Europe.

          The allergenic content of the atmosphere varies according to climate, geography and vegetation. Data on the presence and prevalence of allergenic airborne pollens, obtained from both aerobiological studies and allergological investigations, make it possible to design pollen calendars with the approximate flowering period of the plants in the sampling area. In this way, even though pollen production and dispersal from year to year depend on the patterns of preseason weather and on the conditions prevailing at the time of anthesis, it is usually possible to forecast the chances of encountering high atmospheric allergenic pollen concentrations in different areas. Aerobiological and allergological studies show that the pollen map of Europe is changing also as a result of cultural factors (for example, importation of plants such as birch and cypress for urban parklands), greater international travel (e.g. colonization by ragweed in France, northern Italy, Austria, Hungary etc.) and climate change. In this regard, the higher frequency of weather extremes, like thunderstorms, and increasing episodes of long range transport of allergenic pollen represent new challenges for researchers. Furthermore, in the last few years, experimental data on pollen and subpollen-particles structure, the pathogenetic role of pollen and the interaction between pollen and air pollutants, gave new insights into the mechanisms of respiratory allergic diseases.
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            Herpes simplex virus infections.

            Herpes simplex virus (HSV) is a member of the herpesviridae family. Recognised since ancient Greek times, the virus frequently infects human beings, causing a range of diseases from mild uncomplicated mucocutaneous infection to those that are life threatening. In the past 50 years, substantial advances in our knowledge of the molecular biology of HSV have led to insights into disease pathogenesis and management. This review provides a contemporary interpretation of the biological properties, function, epidemiology, and treatment of HSV diseases.
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              PI3K signalling in inflammation.

              PI3Ks regulate several key events in the inflammatory response to damage and infection. There are four Class I PI3K isoforms (PI3Kα,β,γ,δ), three Class II PI3K isoforms (PI3KC2α, C2β, C2γ) and a single Class III PI3K. The four Class I isoforms synthesise the phospholipid 'PIP3'. PIP3 is a 'second messenger' used by many different cell surface receptors to control cell movement, growth, survival and differentiation. These four isoforms have overlapping functions but each is adapted to receive efficient stimulation by particular receptor sub-types. PI3Kγ is highly expressed in leukocytes and plays a particularly important role in chemokine-mediated recruitment and activation of innate immune cells at sites of inflammation. PI3Kδ is also highly expressed in leukocytes and plays a key role in antigen receptor and cytokine-mediated B and T cell development, differentiation and function. Class III PI3K synthesises the phospholipid PI3P, which regulates endosome-lysosome trafficking and the induction of autophagy, pathways involved in pathogen killing, antigen processing and immune cell survival. Much less is known about the function of Class II PI3Ks, but emerging evidence indicates they can synthesise PI3P and PI34P2 and are involved in the regulation of endocytosis. The creation of genetically-modified mice with altered PI3K signalling, together with the development of isoform-selective, small-molecule PI3K inhibitors, has allowed the evaluation of the individual roles of Class I PI3K isoforms in several mouse models of chronic inflammation. Selective inhibition of PI3Kδ, γ or β has each been shown to reduce the severity of inflammation in one or more models of autoimmune disease, respiratory disease or allergic inflammation, with dual γ/δ or β/δ inhibition generally proving more effective. The inhibition of Class I PI3Ks may therefore offer a therapeutic opportunity to treat non-resolving inflammatory pathologies in humans. This article is part of a Special Issue entitled Phosphoinositides.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                04 March 2021
                2021
                : 12
                : 662686
                Affiliations
                [1] 1Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University , Merelbeke, Belgium
                [2] 2Division of Virology, Department Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University , Utrecht, Netherlands
                [3] 3HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University and Ghent University Hospital , Ghent, Belgium
                [4] 4Shenzhen International Institute for Biomedical Research , Shenzhen, China
                [5] 5DGZ Vlaanderen vzw , Torhout, Belgium
                [6] 6Equipe Veterinary Practice, Equi Focus Point Belgium , Vlamertinge, Belgium
                [7] 7Haras de la vie , Koewacht, Belgium
                [8] 8PERSEUS bvba , Sint Martens Latem, Belgium
                [9] 9Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences , Tabriz, Iran
                [10] 10College of Veterinary Medicine and Agriculture, Addis Ababa University , Bishoftu, Ethiopia
                Author notes

                Edited by: Chunfu Zheng, Fujian Medical University, China

                Reviewed by: Diqiu Liu, Chinese Academy of Agricultural Sciences, China; Yan-Dong Tang, Chinese Academy of Agricultural Sciences, China

                *Correspondence: Kathlyn Laval, kathlyn.laval@ 123456ugent.be

                This article was submitted to Virology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2021.662686
                7970122
                33746936
                b874b40d-904a-4f91-a149-43e59e824810
                Copyright © 2021 Laval, Poelaert, Van Cleemput, Zhao, Vandekerckhove, Gryspeerdt, Garré, van der Meulen, Baghi, Dubale, Zarak, Van Crombrugge and Nauwynck.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 February 2021
                : 15 February 2021
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 119, Pages: 12, Words: 0
                Funding
                Funded by: Universiteit Gent 10.13039/501100004385
                Categories
                Microbiology
                Review

                Microbiology & Virology
                pathogenesis,immune evasion,prevention,therapies,equine herpesvirus type 1
                Microbiology & Virology
                pathogenesis, immune evasion, prevention, therapies, equine herpesvirus type 1

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