ANCHOR-tagged equine herpesvirus 1: A new tool for monitoring viral infection and discovering new antiviral compounds.
Abstract: Equine herpesvirus 1 (EHV-1) is a causative agent of respiratory disorders, abortion and myeloencephalopathy in horses and has an important impact on equine health and economy. Several bacterial artificial chromosomes have already been developed and enabled identification and functional characterization of EHV-1 genes. Unfortunately, little is known about its replication. Here, the ANCHOR system was inserted by targeted homologous recombination into the equine herpesvirus genome. This insertion led to the conversion of EHV-1 DNA to auto-fluorescent spots easily detectable by fluorescence microscopy, and enabled production of an auto-fluorescent EHV-1 ANCHORGFP with tropism and replication kinetic like the parental strain. High resolution imaging allowed first visualization of EHV-1 replication from apparition of first viral genome to large replicative centers, in single cells or inside syncytia. Combined with high content microscopy, EHV-1 ANCHORGFP leads to identification of auranofin and azacytidine-5 as new potential antivirals to treat EHV-1 infection.
Copyright © 2021 Elsevier B.V. All rights reserved.
Publication Date: 2021-05-19 PubMed ID: 34022301DOI: 10.1016/j.jviromet.2021.114194Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research article presents the development of a new tool, dubbed the ANCHOR system, to monitor the infection lifecycle of Equine Herpesvirus 1 (EHV-1), which causes significant disease in horses. This system has also helped identify potential new antiviral treatments for the disease.
Introduction to the ANCHOR System
- Equine herpesvirus 1 (EHV-1) is known to cause various conditions in horses including respiratory disorders, abortion, and myeloencephalopathy, thereby affecting the equine health and the related economic aspects.
- In an effort to better understand the replication and effects of the EHV-1 genome, the researchers integrated a specific system known as ANCHOR into the virus’s genome.
- This was achieved through a process known as targeted homologous recombination.
- The ANCHOR system drives the EHV-1 DNA to transform into auto-fluorescent spots that can be easily observed through fluorescence microscopy.
Implications of the ANCHOR System
- The integration of the ANCHOR system enabled the production of an auto-fluorescent EHV-1 (EHV-1 ANCHORGFP) which replicated at similar rates and with a similar tropism to the original strain.
- High-resolution imaging was used to track the replication of EHV-1 throughout infected cells, from the initial appearance of the viral genome to the formation of large replications centers.
- This detailed imaging helped to understand the infection process and replication stages of the virus, both in single cells and in syncytia (a collection of cells that act as one).
Discovery of New Potential Antivirals
- By utilizing this modified EHV-1 in conjunction with high-content microscopy, the researchers were able to screen and identify potential antiviral treatments for EHV-1.
- Two compounds, auranofin and azacytidine-5, were found to potentially carry antiviral properties and could be new means for treating EHV-1 infection.
- These findings represent the initial steps toward the development of an effective treatment for this viral infection in horses.
Cite This Article
APA
Quentin-Froignant C, Kappler-Gratias S, Top S, Bertagnoli S, Gallardo F.
(2021).
ANCHOR-tagged equine herpesvirus 1: A new tool for monitoring viral infection and discovering new antiviral compounds.
J Virol Methods, 294, 114194.
https://doi.org/10.1016/j.jviromet.2021.114194 Publication
Researcher Affiliations
- NeoVirTech SAS, Centre Pierre Potier, Toulouse, France; IHAP, Université de Toulouse, INRAE, ENVT, Toulouse, France. Electronic address: qfroignant@neovirtech.com.
- NeoVirTech SAS, Centre Pierre Potier, Toulouse, France. Electronic address: skappler@neovirtech.com.
- NeoVirTech SAS, Centre Pierre Potier, Toulouse, France. Electronic address: sokuntheatop@neovirtech.com.
- IHAP, Université de Toulouse, INRAE, ENVT, Toulouse, France. Electronic address: stephane.bertagnoli@envt.fr.
- NeoVirTech SAS, Centre Pierre Potier, Toulouse, France. Electronic address: fgallardo@neovirtech.com.
MeSH Terms
- Animals
- Antiviral Agents / pharmacology
- Chromosomes, Artificial, Bacterial
- Genome, Viral
- Herpesviridae Infections / drug therapy
- Herpesviridae Infections / veterinary
- Herpesvirus 1, Equid / genetics
- Horse Diseases / diagnosis
- Horses
Citations
This article has been cited 1 times.- Nielsen SS, Alvarez J, Bicout DJ, Calistri P, Canali E, Drewe JA, Garin-Bastuji B, Gonzales Rojas JL, Gortázar C, Herskin M, Michel V, Miranda Chueca MÁ, Roberts HC, Padalino B, Pasquali P, Spoolder H, Ståhl K, Calvo AV, Viltrop A, Winckler C, Carvelli A, Paillot R, Broglia A, Kohnle L, Baldinelli F, Van der Stede Y. Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): infection with Equine Herpesvirus-1.. EFSA J 2022 Jan;20(1):e07036.
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