Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process.
Abstract: Equine infectious anemia virus (EIAV) provides a natural model system by which immunological control of lentivirus infections may be studied. To date, no detailed study addressing in parallel both the humoral and cellular immune responses induced in horses upon infection by EIAV has been conducted. Therefore, we initiated the first comprehensive characterization of the cellular and humoral immune responses during clinical progression from chronic disease to inapparent stages of EIAV infection. Using new analyses of antibody avidity and antibody epitope conformation dependence that had not been previously employed in this system, we observed that the humoral immune response to EIAV required a 6- to 8-month period in which to fully mature. During this time frame, EIAV-specific antibody evolved gradually from a population characterized by low-avidity, nonneutralizing, and predominantly linear epitope specificity to an antibody population with an avidity of moderate to high levels, neutralizing activity, and predominantly conformational epitope specificity. Analyses of the cell-mediated immune response to EIAV revealed CD4+ and CD8+ major histocompatibility complex-restricted, EIAV-specific cytotoxic T-lymphocyte (CTL) activity apparent within 3 to 4 weeks postinfection, temporally correlating with the resolution of the primary viremia. After resolution of the initial viremia, EIAV-specific CTL activity differed greatly among the experimentally infected ponies, with some animals having readily detectable CTL activity while others had little measurable CTL activity. Thus, in contrast to the initial viremia, it appeared that no single immune parameter correlated with the resolution of further viremic episodes. Instead, immune control of EIAV infection during the clinically inapparent stage of infection appears to rely on a complex combination of immune system mechanisms to suppress viral replication that effectively functions only after the immune system has evolved to a fully mature state 6 to 8 months postinfection. These findings strongly imply the necessity for candidate EIAV and other lentivirus vaccines to achieve this immune system maturation for efficacious immunological control of lentivirus challenge.
Publication Date: 1997-05-01 PubMed ID: 9094660PubMed Central: PMC191535DOI: 10.1128/JVI.71.5.3840-3852.1997Google Scholar: Lookup
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Summary
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The research focuses on understanding the immune response evoked by equine infectious anemia virus (EIAV) in horses. It observes that a mature immune response, encompassing both cellular and humoral components, takes as long as 6-8 months to fully develop following EIAV infection and is vital for effective control of the virus.
Characterization of Cellular and Humoral Immune Responses
- The study is the first in-depth investigation into the progression of both cellular and humoral immune responses in horses infected with EIAV.
- Utilizing advancements in antibody avidity and epitope conformation dependence analyses, the research identifies a marked change in the humoral immune response over 6-8 months post-infection.
- The initial low-avidity, nonneutralizing antibodies specific to linear epitopes evolve into moderate to high-avidity, neutralizing antibodies mainly targeting conformational epitopes.
Temporal Correlation with Viremia Resolution
- Cell-mediated immune responses, including Major Histocompatibility Complex (MHC)-restricted CD4+ and CD8+ cytotoxic T-lymphocyte (CTL) activities against EIAV, are detected as early as 3 to 4 weeks post-infection, alongside the resolution of primary viremia.
- However, the level of EIAV-specific CTL activity varies widely among horses following the resolution of initial viremia, hinting at the lack of a singular immune parameter responsible for the control of subsequent viremia episodes.
Immune System Maturation and Viral Control
- Control of EIAV infection during the clinically inapparent stage seems to rely on a comprehensive combination of immune mechanisms working to suppress viral replication.
- This control only becomes effective once the immune system has fully matured, which takes 6 to 8 months post-infection, underlining the necessity for potential EIAV vaccines to encourage this immune maturation for effective control of lentivirus.
Cite This Article
APA
Hammond SA, Cook SJ, Lichtenstein DL, Issel CJ, Montelaro RC.
(1997).
Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process.
J Virol, 71(5), 3840-3852.
https://doi.org/10.1128/JVI.71.5.3840-3852.1997 Publication
Researcher Affiliations
- Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pennsylvania 15261, USA.
MeSH Terms
- Animals
- Antibodies, Viral / blood
- Antibody Affinity
- CD4-Positive T-Lymphocytes / immunology
- Equine Infectious Anemia / immunology
- Horses
- Immunoglobulin G / blood
- Lymphocyte Activation
- Major Histocompatibility Complex
- Protein Conformation
- T-Lymphocytes, Cytotoxic / immunology
Grant Funding
- 5RO1 AI25810 / NIAID NIH HHS
- 5T32 AI07487 / NIAID NIH HHS
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- Fraser DG, Oaks JL, Brown WC, McGuire TC. Identification of broadly recognized, T helper 1 lymphocyte epitopes in an equine lentivirus. Immunology 2002 Mar;105(3):295-305.
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