Immune responses and viral replication in long-term inapparent carrier ponies inoculated with equine infectious anemia virus.
Abstract: Persistent infection of equids by equine infectious anemia virus (EIAV) is typically characterized by a progression during the first year postinfection from chronic disease with recurring disease cycles to a long-term asymptomatic infection that is maintained indefinitely. The goal of the current study was to perform a comprehensive longitudinal analysis of the course of virus infection and development of host immunity in experimentally infected horses as they progressed from chronic disease to long-term inapparent carriage. We previously described the evolution of EIAV genomic quasispecies (C. Leroux, C. J. Issel, and R. C. Montelaro, J. Virol. 71:9627-9639, 1997) and host immune responses (S. A. Hammond, S. J. Cook, D. L. Lichtenstein, C. J. Issel, and R. C. Montelaro, J. Virol. 71:3840-3852, 1997) in four experimentally infected ponies during sequential disease episodes associated with chronic disease during the first 10 months postinfection. In the current study, we extended the studies of these experimentally infected ponies to 3 years postinfection to characterize the levels of virus replication and development of host immune responses associated with the progression from chronic disease to long-term inapparent infection. The results of these studies revealed over a 10(3)-fold difference in the steady-state levels of plasma viral RNA detected during long-term inapparent infection that correlated with the severity of chronic disease, indicating different levels of control of virus replication during long-term inapparent infections. Detailed analyses of antibody and cellular immune responses in all four ponies over the 3-year course of infection revealed a similar evolution during the first year postinfection of robust humoral and cellular immunity that then remained relatively constant during long-term inapparent infection. These observations indicate that immune parameters that have previously been correlated with EIAV vaccine protection fail to provide reliable immune correlates of control of virus replication or clinical outcome in experimental infections. Thus, these data emphasize the differences between immunity to virus exposure and immune control of an established viral infection and further emphasize the need to develop and evaluate novel immunoassays to define reliable immune correlates to vaccine and infection immunity, respectively.
Publication Date: 2000-06-14 PubMed ID: 10846078PubMed Central: PMC112093DOI: 10.1128/jvi.74.13.5968-5981.2000Google 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 aims to provide a detailed analysis of the development of host immunity and the effect of virus replication in horses experimentally infected with equine infectious anemia virus (EIAV) as they transition from chronic disease to long-term asymptomatic status. The results highlight a stark contrast between immune response associated with virus exposure and immune control of a persistent viral infection, necessitating the development of novel immune tests.
Overview of Research
- The study focuses on the longitudinal analysis of immune responses and virus replication in horses experimentally infected with EIAV. The aim was to study the transition from a chronic disease state with recurring disease cycles to a persistent, asymptomatic infection.
- The research represents an extension of previous studies done on experimentally infected ponies upon extending these to 3 years post-infection. Accordingly, it provides insights into both the short-term and long-term ramifications of EIAV infection in horses and the corresponding evolution of their immune responses.
Key Findings
- There is a significant disparity (over a 10(3)-fold difference) in plasma viral RNA levels detected during long-term asymptomatic infection. This discrepancy aligns with the severity of the chronic disease identifying varying levels of virus replication control during different infection statuses.
- A robust humoral (antibody-related) and cellular immune response evolves during the first year post-infection, which then stays comparatively constant throughout long-term asymptomatic infection.
- These observations underline the differences between immune responses toward virus exposure and immune control of an already established viral infection. This inconsistency has implications for vaccine development and disease control strategies.
Implications
- The results imply that immune responses that previously correlated with EIAV vaccine protection are not reliable indicators of virus replication control or clinical outcome in experimental infections.
- This suggests the need for the development and evaluation of new immunoassays to adequately define immune correlates to vaccine and infection immunity, respectively. This is crucial in advancing our understanding of immune responses in horses to EIAV and yield more effective disease control strategies.
Cite This Article
APA
Hammond SA, Li F, McKeon BM, Cook SJ, Issel CJ, Montelaro RC.
(2000).
Immune responses and viral replication in long-term inapparent carrier ponies inoculated with equine infectious anemia virus.
J Virol, 74(13), 5968-5981.
https://doi.org/10.1128/jvi.74.13.5968-5981.2000 Publication
Researcher Affiliations
- Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, PA 15261, USA.
MeSH Terms
- Animals
- Antibodies, Viral / blood
- Antibodies, Viral / immunology
- Antibody Affinity
- Equine Infectious Anemia / immunology
- Equine Infectious Anemia / physiopathology
- Equine Infectious Anemia / virology
- Horses
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / immunology
- Infectious Anemia Virus, Equine / physiology
- Neutralization Tests
- RNA, Viral / blood
- Reverse Transcriptase Polymerase Chain Reaction / methods
- T-Lymphocytes, Cytotoxic / immunology
- Time Factors
- Viral Envelope Proteins / immunology
- Virus Replication / immunology
Grant Funding
- T32 AI007487 / NIAID NIH HHS
- 5RO1 AI25810 / NIAID NIH HHS
- 5T32 AI07487 / NIAID NIH HHS
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