Transient immune suppression of inapparent carriers infected with a principal neutralizing domain-deficient equine infectious anaemia virus induces neutralizing antibodies and lowers steady-state virus replication.
Abstract: The genetic variation of equine infectious anaemia virus (EIAV) clearly affects the antigenic properties of the viral envelope; however, effects on immunogenicity remain undefined, although widely assumed. Here, the immunogenicity is reported of a novel, neutralization-resistant, pony-isolate envelope EIAV(PV564DeltaPND) that contains a 14-residue deletion in the designated principal neutralizing domain (PND) of the gp90 protein. Two ponies inoculated with a chimeric virus, EIAV(DeltaPND), containing the EIAV(PV564DeltaPND) envelope in a reference provirus strain, remained asymptomatic through 14 months post-inoculation, producing high steady-state levels of envelope-specific antibodies but no detectable serum-neutralizing antibodies. Consequent dexamethasone-induced immune suppression produced characteristic EIA that resolved concomitantly with the development of high-titre, strain-specific, neutralizing antibodies and a 100-fold reduction in steady-state virus loads. These results demonstrate: natural variations in the EIAV envelope have profound effects on both antigenic and immunogenic properties; the PND is not required for neutralizing antibody responses; and transient immune suppression can enhance established host immunity to achieve more effective control of steady-state lentivirus replication.
Publication Date: 2002-05-25 PubMed ID: 12029150DOI: 10.1099/0022-1317-83-6-1353Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This study focuses on the impact of immune suppression on the equine infectious anemia virus (EIAV), a variant that contains a deletion mutation in the principal neutralizing domain (PND) of the gp90 protein, which is assumed to change the immunogenic characteristics. Researchers found that after temporarily suppressing the immune system, the body produced more neutralizing antibodies and significantly reduced the virus’ replication.
Overview of Research Methodology
- Initially, two ponies were inoculated with a chimeric virus, EIAV(ΔPND), that contained the new envelope version of EIAV(PV564ΔPND) in a reference provirus strain.
- Despite having elevated levels of envelope-specific antibodies, the ponies did not produce any notable serum-neutralizing antibodies for a period of 14 months and remained asymptomatic throughout.
- Following this, the researchers tried to induce the anaemia by using dexamethasone-induced immune suppression.
Key Findings
- After the immune suppression, the anaemia did develop but resolved simultaneously with the production of high-titre, strain-specific, neutralizing antibodies.
- In addition, a significant decrease in the steady-state replication of virus – by a factor of 100 – was noticed.
Implications of the Study
- The results demonstrate that natural variations in the EIAV envelope can have significant effects on both antigenic and immunogenic properties.
- The PND part of the gp90 protein is not necessary for a neutralizing antibody response to occur. This counters previous assumptions and widens the scope for future study about viral properties.
- Temporary immune suppression seems to lead to enhanced immunity, resulting in better control over steady-state lentivirus replication.
Cite This Article
APA
Craigo JK, Leroux C, Howe L, Steckbeck JD, Cook SJ, Issel CJ, Montelaro RC.
(2002).
Transient immune suppression of inapparent carriers infected with a principal neutralizing domain-deficient equine infectious anaemia virus induces neutralizing antibodies and lowers steady-state virus replication.
J Gen Virol, 83(Pt 6), 1353-1359.
https://doi.org/10.1099/0022-1317-83-6-1353 Publication
Researcher Affiliations
- Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA1.
- Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA1.
- Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA1.
- Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA1.
- Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546, USA2.
- Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546, USA2.
- Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA1.
MeSH Terms
- Amino Acid Sequence
- Animals
- Antibodies, Viral / biosynthesis
- Antibodies, Viral / immunology
- Carrier State / immunology
- Carrier State / veterinary
- Dexamethasone / pharmacology
- Equine Infectious Anemia / immunology
- Equine Infectious Anemia / virology
- Gene Deletion
- Glycoproteins / genetics
- Glycoproteins / immunology
- Horses
- Immunocompromised Host
- Immunosuppressive Agents / pharmacology
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / physiology
- Molecular Sequence Data
- RNA, Viral / analysis
- Recombination, Genetic
- Sequence Alignment
- Viral Envelope Proteins / genetics
- Viral Envelope Proteins / immunology
- Virus Replication
Grant Funding
- 2P41 RR 06009 / NCRR NIH HHS
- R01 AI 25850 / NIAID NIH HHS
Citations
This article has been cited 18 times.- 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.
- Liu Q, Wang XF, Ma J, He XJ, Wang XJ, Zhou JH. Characterization of Equine Infectious Anemia Virus Integration in the Horse Genome. Viruses 2015 Jun 19;7(6):3241-60.
- Liu C, Cook SJ, Craigo JK, Cook FR, Issel CJ, Montelaro RC, Horohov DW. Epitope shifting of gp90-specific cellular immune responses in EIAV-infected ponies. Vet Immunol Immunopathol 2014 Oct 15;161(3-4):161-9.
- Craigo JK, Montelaro RC. Lessons in AIDS vaccine development learned from studies of equine infectious, anemia virus infection and immunity. Viruses 2013 Dec 2;5(12):2963-76.
- Craigo JK, Ezzelarab C, Cook SJ, Chong L, Horohov D, Issel CJ, Montelaro RC. Envelope determinants of equine lentiviral vaccine protection. PLoS One 2013;8(6):e66093.
- Issel CJ, Scicluna MT, Cook SJ, Cook RF, Caprioli A, Ricci I, Rosone F, Craigo JK, Montelaro RC, Autorino GL. Challenges and proposed solutions for more accurate serological diagnosis of equine infectious anaemia. Vet Rec 2013 Feb 23;172(8):210.
- Craigo JK, Ezzelarab C, Montelaro RC. Development of a high throughput, semi-automated, infectious center cell-based ELISA for equine infectious anemia virus. J Virol Methods 2012 Nov;185(2):221-7.
- Liu C, Cook FR, Cook SJ, Craigo JK, Even DL, Issel CJ, Montelaro RC, Horohov DW. The determination of in vivo envelope-specific cell-mediated immune responses in equine infectious anemia virus-infected ponies. Vet Immunol Immunopathol 2012 Aug 15;148(3-4):302-10.
- 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.
- Craigo JK, Barnes S, Cook SJ, Issel CJ, Montelaro RC. Divergence, not diversity of an attenuated equine lentivirus vaccine strain correlates with protection from disease. Vaccine 2010 Nov 29;28(51):8095-104.
- Taylor SD, Leib SR, Carpenter S, Mealey RH. Selection of a rare neutralization-resistant variant following passive transfer of convalescent immune plasma in equine infectious anemia virus-challenged SCID horses. J Virol 2010 Jul;84(13):6536-48.
- Craigo JK, Barnes S, Zhang B, Cook SJ, Howe L, Issel CJ, Montelaro RC. An EIAV field isolate reveals much higher levels of subtype variability than currently reported for the equine lentivirus family. Retrovirology 2009 Oct 20;6:95.
- Craigo JK, Zhang B, Barnes S, Tagmyer TL, Cook SJ, Issel CJ, Montelaro RC. Envelope variation as a primary determinant of lentiviral vaccine efficacy. Proc Natl Acad Sci U S A 2007 Sep 18;104(38):15105-10.
- Boissin-Quillon A, Piau D, Leroux C. In silico segmentations of lentivirus envelope sequences. BMC Bioinformatics 2007 Mar 21;8:99.
- Craigo JK, Durkin S, Sturgeon TJ, Tagmyer T, Cook SJ, Issel CJ, Montelaro RC. Immune suppression of challenged vaccinates as a rigorous assessment of sterile protection by lentiviral vaccines. Vaccine 2007 Jan 15;25(5):834-45.
- Craigo JK, Li F, Steckbeck JD, Durkin S, Howe L, Cook SJ, Issel C, Montelaro RC. Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy. J Virol 2005 Mar;79(5):2666-77.
- Howe L, Leroux C, Issel CJ, Montelaro RC. Equine infectious anemia virus envelope evolution in vivo during persistent infection progressively increases resistance to in vitro serum antibody neutralization as a dominant phenotype. J Virol 2002 Nov;76(21):10588-97.
- Witkowska-Piłaszewicz O, Malin K, Dąbrowska I, Grzędzicka J, Ostaszewski P, Carter C. Immunology of Physical Exercise: Is Equus caballus an Appropriate Animal Model for Human Athletes?. Int J Mol Sci 2024 May 10;25(10).
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