Equine infectious anemia virus envelope evolution in vivo during persistent infection progressively increases resistance to in vitro serum antibody neutralization as a dominant phenotype.
Abstract: Equine infectious anemia virus (EIAV) infection of horses is characterized by well-defined waves of viremia associated with the sequential evolution of distinct viral populations displaying extensive envelope gp90 variation; however, a correlation of in vivo envelope evolution with in vitro serum neutralization phenotype remains undefined. Therefore, the goal of the present study was to utilize a previously defined panel of natural variant EIAV envelope isolates from sequential febrile episodes to characterize the effects of envelope variation during persistent infection on viral neutralization phenotypes and to define the determinants of EIAV envelope neutralization specificity. To assess the neutralization phenotypes of the sequential EIAV envelope variants, we determined the sensitivity of five variant envelopes to neutralization by a longitudinal panel of immune serum from the source infected pony. The results indicated that the evolution of the EIAV envelope sequences observed during sequential febrile episodes produced an increasingly neutralization-resistant phenotype. To further define the envelope determinants of EIAV neutralization specificity, we examined the neutralization properties of a panel of chimeric envelope constructs derived from reciprocal envelope domain exchanges between selected neutralization-sensitive and neutralization-resistant envelope variants. These results indicated that the EIAV gp90 V3 and V4 domains individually conferred serum neutralization resistance while other envelope segments in addition to V3 and V4 were evidently required for conferring total serum neutralization sensitivity. These data clearly demonstrate for the first time the influence of sequential gp90 variation during persistent infection in increasing envelope neutralization resistance, identify the gp90 V3 and V4 domains as the principal determinants of antibody neutralization resistance, and indicate distinct complex cooperative envelope domain interactions in defining sensitivity to serum antibody neutralization.
Publication Date: 2002-10-09 PubMed ID: 12368301PubMed Central: PMC136617DOI: 10.1128/jvi.76.21.10588-10597.2002Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research investigates how the Equine Infectious Anemia Virus (EIAV) evolves in horses over time to become increasingly resistant to immune system responses. Its findings point to specific parts of the virus—known as the gp90 V3 and V4 domains—as the main contributors to this resistance, increasing our understanding of this disease and potentially informing future treatment strategies.
Understanding EIAV Evolution and Resistance
The Equine Infectious Anemia Virus (EIAV) presents in horses in waves of viremia (viral presence in the bloodstream), each characterized by different viral populations showcasing various envelope variations. These variations in the envelope of the virus, specifically gp90, were found to increase the virus’s resistance to neutralization by antibodies in the horse’s serum over time, signifying an evolution of the virus within the host. This progression was tracked using a series of natural EIAV envelope variants taken from sequential episodes of fever in the infected horse.
- The panel of natural EIAV envelope variants was used to study the effects of envelope variations on viral neutralization.
- Five different envelope variants were assessed for their sensitivity to neutralization by using a series of immune sera from the source horse. Results showed that increased envelope sequence variations over time resulted in an increasingly neutralization-resistant phenotype.
Identifying Key Envelope Variants
In order to determine the specific envelope properties that gave rise to neutralization resistance, the researchers examined a series of chimera constructs. These constructs were the result of domain exchanges between different envelopes, ranging from neutralization-sensitive to neutralization-resistant variants.
- The gp90 V3 and V4 domains within the EIAV envelope were identified as the main contributors to serum neutralization resistance.
- However, other envelope segments alongside V3 and V4 also played a crucial part in total serum neutralization sensitivity, suggesting that there a complex interplay of envelope attributes that influence sensitivity to serum antibody neutralization.
The research concludes by establishing the gp90 V3 and V4 domains’ crucial role in antibody neutralization resistance and noting the complicated interaction of envelope domain elements in defining sensitivity to serum antibody neutralization. These findings provide critical insights into EIAV evolution during persistent infection, enhancing our understanding of the virus’s survival mechanisms and informing potential countermeasures.
Cite This Article
APA
Howe L, Leroux C, Issel CJ, Montelaro RC.
(2002).
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, 76(21), 10588-10597.
https://doi.org/10.1128/jvi.76.21.10588-10597.2002 Publication
Researcher Affiliations
- Department of Infectious Disease and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
MeSH Terms
- Amino Acid Sequence
- Animals
- Antibodies, Viral / blood
- Antibodies, Viral / immunology
- Directed Molecular Evolution
- Disease Progression
- Epitope Mapping
- Epitopes, B-Lymphocyte / genetics
- Epitopes, B-Lymphocyte / immunology
- Equine Infectious Anemia / physiopathology
- Equine Infectious Anemia / virology
- Glycoproteins / genetics
- Glycoproteins / immunology
- Horses
- Immunodominant Epitopes / genetics
- Immunodominant Epitopes / immunology
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / immunology
- Molecular Sequence Data
- Neutralization Tests
- Phenotype
- Viral Envelope Proteins / genetics
- Viral Envelope Proteins / immunology
Grant Funding
- R01 AI025850 / NIAID NIH HHS
- R01 AI25850 / NIAID NIH HHS
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