Combined amino acid mutations occurring in the envelope closely correlate with pathogenicity of EIAV.
Abstract: The Chinese equine infectious anemia virus (EIAV) donkey-leukocyte attenuated vaccine (DLV) provides a unique natural model system to study the attenuation mechanism and immunological control of lentivirus replication. Critical consensus mutations were identified between virulent Chinese EIAV strains and vaccine strains. Based on a full-length infectious clone of EIAV vaccine strain pLGFD3, two molecular clones, mFD5-4-7 and mFD7-2-11, were successfully constructed, in which 4 and 6 critical consensus mutations in the env gene of the vaccine strain were point-mutated to the wild-type sequence, respectively by an overlap PCR mutagenesis strategy. The infectivity, virulence, and pathogenesis of the constructed clones were investigated in vitro using a reverse transcriptase assay, an indirect immunofluorescence assay, observation of cytopathogenic effect, and virion observation as well as in vivo by inoculation of animals with the resulting infectious clones. The pathogenic symptoms in horses inoculated with mFD7-2-11 were more severe than those inoculated with mFD5-4-7, whereas no pathogenic symptoms were detected in animals inoculated with their parental clone pLGFD3 strain. The results indicate that the consensus mutation residues of the env region involved in this study play significant roles in the virulence and pathogenicity of EIAV. This will contribute to the elucidation of the attenuating and protective mechanisms of the Chinese EIAV vaccine.
Publication Date: 2006-02-26 PubMed ID: 16502285DOI: 10.1007/s00705-005-0718-3Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research examines how specific mutations in the envelope of the equine infectious anemia virus (EIAV) influence the virus’s pathogenicity, using a unique Chinese EIAV vaccine model.
Study Objectives and Methodology
- The purpose of this research was to identify the specific mutations in the EIAV envelope that impact its virulence and pathogenicity. The researchers set out to understand why some strains of EIAV are more virulent than others.
- In their study, they engineered two different clones of EIAV strain pLGFD3. These clones had several key mutations in their env genes – 4 mutations in the mFD5-4-7 clone and 6 mutations in the mFD7-2-11 clone – that were added using an overlapping PCR mutagenesis strategy.
- The clones were then tested both in vitro (in reverse transcriptase assays, immunofluorescence assays, and through observation of cytopathogenic effects and virions) and in vivo (by inoculating animals with these infectious clones).
Findings and Conclusions
- The researchers found distinct differences in virulence and pathogenicity between the two clones and the pLGFD3 parent strain. The horses inoculated with the clone mFD7-2-11 exhibited more severe pathogenic symptoms than the clone mFD5-4-7. Animals inoculated with the parent strain, pLGFD3, showed no pathogenic symptoms.
- These results highlighted the importance of env gene consensus mutation residues in determining the virulence and pathogenicity of EIAV. The greater the number of mutations, the more severe the symptoms experienced by the hosts.
- This research helps steer future work towards understanding the attenuation mechanism of the EIAV vaccine. This understanding will prove useful in enhancing the current vaccine’s effectiveness or in developing new vaccines targeting this equine disease.
Cite This Article
APA
Liang H, He X, Shen RX, Shen T, Tong X, Ma Y, Xiang WH, Zhang XY, Shao YM.
(2006).
Combined amino acid mutations occurring in the envelope closely correlate with pathogenicity of EIAV.
Arch Virol, 151(7), 1387-1403.
https://doi.org/10.1007/s00705-005-0718-3 Publication
Researcher Affiliations
- State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, PR China.
MeSH Terms
- Amino Acid Sequence
- Amino Acid Substitution
- Animals
- Body Temperature
- Cell Line
- Cytopathogenic Effect, Viral
- Disease Models, Animal
- Equidae
- Equine Infectious Anemia / physiopathology
- Equine Infectious Anemia / virology
- Fluorescent Antibody Technique, Direct
- Gene Products, env / chemistry
- Gene Products, env / genetics
- Genes, env
- Horses
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / pathogenicity
- Microscopy, Electron, Transmission
- Molecular Sequence Data
- Platelet Count
- Point Mutation
- Sequence Alignment
- Vaccines, Attenuated / genetics
- Viral Vaccines / genetics
- Virulence / genetics
Citations
This article has been cited 13 times.- Shao Y, Liu Y, Hao Y, Xu J, Li T, Wu H, Zhang T, Wu L, Wang S, Li D, Ren L, Wu Y. China CDC's HIV/AIDS Vaccine Efforts, from Basic Research to Clinical Studies.. China CDC Wkly 2020 Nov 27;2(48):929-932.
- Wang HN, Rao D, Fu XQ, Hu MM, Dong JG. Equine infectious anemia virus in China.. Oncotarget 2018 Jan 2;9(1):1356-1364.
- Han X, Zhang P, Yu W, Xiang W, Li X. Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies.. Virus Genes 2016 Dec;52(6):814-822.
- Wang XF, Lin YZ, Li Q, Liu Q, Zhao WW, Du C, Chen J, Wang X, Zhou JH. Genetic Evolution during the development of an attenuated EIAV vaccine.. Retrovirology 2016 Feb 3;13:9.
- Duan L, Du J, Liu X. Insights into vaccine development for acquired immune deficiency syndrome from crystal structures of human immunodeficiency virus-1 gp41 and equine infectious anemia virus gp45.. Protein Sci 2015 Oct;24(10):1549-59.
- Du J, Wang X, Ma J, Wang J, Qin Y, Zhu C, Liu F, Shao Y, Zhou J, Qiao W, Liu X. Structural and biochemical insights into the V/I505T mutation found in the EIAV gp45 vaccine strain.. Retrovirology 2014 Mar 21;11:26.
- Meng Q, Lin Y, Ma J, Ma Y, Zhao L, Li S, Yang K, Zhou J, Shen R, Zhang X, Shao Y. A pilot study comparing the development of EIAV Env-specific antibodies induced by DNA/recombinant vaccinia-vectored vaccines and an attenuated Chinese EIAV vaccine.. Viral Immunol 2012 Dec;25(6):477-84.
- Yuan Q, Liu C, Liang Z, Chen X, Diao D, Kong X. The comparison of genetic variation in the envelope protein between various immunodeficiency viruses and equine infectious anemia virus.. Virol Sin 2012 Aug;27(4):241-7.
- Sun PL, Lv SX, Zhou JH, Liu XQ. Cloning, expression and preliminary crystallographic analysis of the equine infectious anaemia virus (EIAV) gp45 ectodomain.. Acta Crystallogr Sect F Struct Biol Cryst Commun 2011 Apr 1;67(Pt 4):482-5.
- Wang X, Wang S, Lin Y, Jiang C, Ma J, Zhao L, Lv X, Wang F, Shen R, Zhou J. Unique evolution characteristics of the envelope protein of EIAV(LN₄₀), a virulent strain of equine infectious anemia virus.. Virus Genes 2011 Apr;42(2):220-8.
- Liu L, Wan Y, Wu L, Sun J, Li H, Li H, Ma L, Shao Y. Broader HIV-1 neutralizing antibody responses induced by envelope glycoprotein mutants based on the EIAV attenuated vaccine.. Retrovirology 2010 Sep 1;7:71.
- Qi X, Wang X, Wang S, Lin Y, Jiang C, Ma J, Zhao L, Lv X, Shen R, Wang F, Kong X, Su Z, Zhou J. Genomic analysis of an effective lentiviral vaccine-attenuated equine infectious anemia virus vaccine EIAV FDDV13.. Virus Genes 2010 Aug;41(1):86-98.
- Wei L, Fan X, Lu X, Zhao L, Xiang W, Zhang X, Xue F, Shao Y, Shen R, Wang X. Genetic variation in the long terminal repeat associated with the transition of Chinese equine infectious anemia virus from virulence to avirulence.. Virus Genes 2009 Apr;38(2):285-8.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
