Characterization of Equine Infectious Anemia Virus Long Terminal Repeat Quasispecies In Vitro and In Vivo.
Abstract: The equine infectious anemia virus (EIAV) attenuated vaccine was developed by long-term passaging of a field-isolated virulent strain in cross-species hosts, followed by successive cultivation in cells To explore the molecular mechanism underlying the evolution of the EIAV attenuated vaccine, a systematic study focusing on long-terminal-repeat (LTR) variation in numerous virus strains ranging from virulent EIAV to attenuated EIAV was performed over time both and Two hypervariable regions were identified within the U3 region in the enhancer region (EHR) and the negative regulatory element (NRE) and within the R region in the transcription start site (TSS) and the Tat-activating region (TAR). Among these sites, variation in the U3 region resulted in the formation of additional transcription factor binding sites; this variation of the -adapted strains was consistent with the loss of pathogenicity. Notably, the same LTR variation pattern was observed both and Generally, the LTR variation in both the attenuated virus and the virulent strain fluctuated over time Interestingly, the attenuated-virus-specific LTR variation was also detected in horses infected with the virulent strain, supporting the hypothesis that the evolution of an attenuated virus might have involved branching from EIAV quasispecies. This hypothesis was verified by phylogenetic analysis. The present systematic study examining the molecular evolution of attenuated EIAV from EIAV quasispecies may provide an informative model reflecting the evolution of similar lentiviruses. The attenuated EIAV vaccine was the first lentiviral vaccine used to successfully control for equine infectious anemia in China. This vaccine provides an important reference for studying the relationship between EIAV gene variation and changes in biological characteristics. Importantly, the vaccine provides a model for the investigation of lentiviral quasispecies evolution. This study followed the "natural" development of the attenuated EIAV vaccine by use of a systematic analysis of LTR evolution and The results revealed that the increase in LTR variation with passaging was accompanied by a decrease in virulence, which indicated that LTR variability might parallel the attenuation of virulence. Interestingly, the attenuated-virus-specific LTR variation was also detected in virulent-strain-infected horses, a finding consistent with those of previous investigations of and evolution. Therefore, we present a hypothesis that the evolution of the attenuated virus may involve branching from EIAV quasispecies present .
Copyright © 2018 Wang et al.
Publication Date: 2018-03-28 PubMed ID: 29386282PubMed Central: PMC5874411DOI: 10.1128/JVI.02150-17Google Scholar: Lookup
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Summary
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The research explores the molecular changes over time that occur in the equine infectious anemia virus (EIAV), leading to the development of an attenuated vaccine. The study identifies areas of significant variation in the virus and suggests that this variation might be linked to the loss of pathogenicity and the evolution of the vaccine.
Study Method and Findings
- In this study, the scientists carried out a systematic analysis of the long-terminal-repeat (LTR) variation in several strains of EIAV. These strains ranged from virulent (disease-causing) to attenuated (weakened).
- The research identified two regions within the LTR section of the virus, namely the enhancer region (EHR) and negative regulatory element (NRE) in the U3 region, and the transcription start site (TSS) and Tat-activating region (TAR) in the R region, that were highly variable.
- This variation in the U3 region led to the formation of extra sites for transcription factor binding—proteins that control the rate of transcription of genetic information from DNA to messenger RNA. This was consistent in cell-adapted strains of the virus and matched with the loss of pathogenicity, suggesting that these changes might be responsible for the virus’s transition from virulent to attenuated.
Link to Attenuated Vaccine
- Importantly, the research found that the pattern of LTR variation observed in cell-cultured viruses was also present in viruses drawn directly from infected horses. This was true for both the virulent and attenuated versions of the virus.
- This suggests that the changes identified may have played a role in the evolution of the attenuated EIAV vaccine, a vaccine developed through long-term passage of a virulent EIAV strain in cross-species hosts. The evolution likely involved branching from the EIAV ‘quasispecies’—a group of viruses related through a similar mutation or mutations.
Broader Significance
- The implications of this research extend beyond EIAV alone. As EIAV is a lentivirus—a group of viruses that includes HIV—understanding the variances in its genes and the relationship with changes in its biological characteristics could provide useful insights into the evolution of similar viruses and their potential vaccines.
Cite This Article
APA
Wang XF, Liu Q, Wang YH, Wang S, Chen J, Lin YZ, Ma J, Zhou JH, Wang X.
(2018).
Characterization of Equine Infectious Anemia Virus Long Terminal Repeat Quasispecies In Vitro and In Vivo.
J Virol, 92(8), e02150-17.
https://doi.org/10.1128/JVI.02150-17 Publication
Researcher Affiliations
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin, China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin, China.
- Department of Geriatrics and Gerontology, First Affiliated Hospital of Harbin Medical University, Harbin, China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin, China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin, China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin, China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin, China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin, China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin, China wangxiaojun@caas.cn.
MeSH Terms
- Animals
- Equine Infectious Anemia / genetics
- Equine Infectious Anemia / metabolism
- Evolution, Molecular
- Horses
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / metabolism
- Terminal Repeat Sequences
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Citations
This article has been cited 9 times.- Wang XF, Wang YH, Bai B, Zhang M, Chen J, Zhang X, Gao M, Wang X. Truncation of the Cytoplasmic Tail of Equine Infectious Anemia Virus Increases Virion Production by Improving Env Cleavage and Plasma Membrane Localization. J Virol 2021 Nov 9;95(23):e0108721.
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