A reverse genetics system of African horse sickness virus reveals existence of primary replication.
Abstract: African horse sickness virus (AHSV), a member of the orbivirus genus of the family Reoviridae, is an insect-vectored pathogen of horses of concern to the equine industry. Studies on AHSV replication and pathogenesis have been hampered by the lack of reverse genetics allowing targeted mutation of viral genomes. We demonstrate that AHSV single-stranded RNA synthesized in vitro (core transcripts) is infectious and that there are distinct primary and secondary stages of the replication cycle. Transfection with a mixture of core transcripts from two different serotypes or a mixture of core transcripts and a T7 derived transcript resulted in the recovery of reassortant viruses. Recovery of infectious ASHV from nucleic acid will benefit investigation of the virus and the generation of attenuated vaccines.
Copyright (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication Date: 2010-06-26 PubMed ID: 20600010DOI: 10.1016/j.febslet.2010.06.030Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The researchers’ work focuses on the African horse sickness virus (AHSV), a deadly virus affecting horses. They developed a reverse genetics system that allows them to understand the replication and pathogenesis of AHSV by generating targeted mutations on its genomes.
Understanding AHSV and Its Significance
- The study explores the African horse sickness virus (AHSV), which belongs to the orbivirus genus of the family Reoviridae. This virus is a significant concern to the equine industry as it is a pathogen of horses transmitted by insects.
- Understanding this virus’ characteristics, replication process, and pathogenesis is vital due to its impact on the equine industry. However, these studies have been obstructed due to the absence of reverse genetics, a method needed to generate targeted viral genome mutations.
Introduction of a Reverse Genetics System
- The scientists developed a reverse genetics system for AHSV. Reverse genetics is an innovative process that permits scientists to comprehend the function of a gene by analyzing the phenotypic effects of specific engineered gene sequences. Using this method, they could explore the impact of targeted alterations or mutations in the AHSV genomes.
- They further exhibited that the AHSV single-stranded RNA synthesized in vitro (core transcripts) is infectious. This suggests that AHSV can be propagated in an artificial environment outside of its natural host, an essential step in understanding the virus better.
Stages of AHSV Replication Cycle
- The research identified primary and secondary stages of the AHSV replication cycle. This could provide critical insights into how the virus proliferates and the stages at which it could potentially be interrupted in future research.
- Through transfection, they mixed core transcripts from two different serotypes or a blend of core transcripts and a T7 derived transcript that resulted in the recovery of reassortant viruses. This demonstrates the mechanism by which AHSV possibly evolves and adapts through recombination events.
Future Applications of the Research
- The successful recovery of infectious AHSV from nucleic acid will open new avenues for further exploration of the virus’s nature and behaviors. This is a crucial step for the development of strategies against AHSV.
- Moreover, this research could pave the way for the production of attenuated vaccines. An attenuated vaccine utilizes a weakened form of the germ that causes a disease; hence, understanding the genetic manipulation of AHSV may lead to the creation of a more effective vaccine against it.
Cite This Article
APA
Matsuo E, Celma CC, Roy P.
(2010).
A reverse genetics system of African horse sickness virus reveals existence of primary replication.
FEBS Lett, 584(15), 3386-3391.
https://doi.org/10.1016/j.febslet.2010.06.030 Publication
Researcher Affiliations
- Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
MeSH Terms
- African Horse Sickness Virus / genetics
- African Horse Sickness Virus / isolation & purification
- African Horse Sickness Virus / physiology
- African Horse Sickness Virus / ultrastructure
- Animals
- Cell Line
- DNA, Complementary / genetics
- Gene Expression Regulation, Viral
- Genetic Techniques
- Genome, Viral / genetics
- RNA, Messenger / genetics
- RNA, Messenger / metabolism
- RNA, Viral / genetics
- Reassortant Viruses / classification
- Reassortant Viruses / genetics
- Reassortant Viruses / physiology
- Serotyping
- Transfection
- Virion / isolation & purification
- Virion / ultrastructure
- Virus Replication / physiology
Grant Funding
- BB/F007159/1 / Biotechnology and Biological Sciences Research Council
- BB/F02049X/1 / Biotechnology and Biological Sciences Research Council
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