Immune selection of equine infectious anemia virus env variants during the long-term inapparent stage of disease.
Abstract: The principal neutralizing domain (PND) of equine infectious anemia virus (EIAV) is located in the V3 region of SU. Genetic variation in the PND is considered to play an important role in immune escape and EIAV persistence; however, few studies have characterized genetic variation in SU during the inapparent stage of disease. To better understand the mechanisms of virus persistence, we undertook a longitudinal study of SU variation in a pony experimentally inoculated with the virulent EIAV(Wyo). Viral RNA isolated from the inoculum and from sequential sera samples was amplified by RT-PCR, cloned, and individual clones were sequenced. Of the 147 SU clones obtained, we identified 71 distinct V3 variants that partitioned into five major non-overlapping groups, designated PND-1 to PND-5, which segregated with specific stages of clinical disease. Genotypes representative of each group were inserted into an infectious molecular clone, and chimeric viruses were tested for susceptibility to neutralization by autologous sera from successive times post-infection. Overall, there was a trend for increasing resistance to neutralizing antibody during disease progression. The PND genotype associated with recrudescence late in infection was resistant to both type-specific and broadly neutralizing antibody, and displayed a reduced replication phenotype in vitro. These findings indicate that neutralizing antibody exerts selective pressure throughout infection and suggest that viral strategies of immune evasion and persistence change in the face of an evolving and maturing host immune response.
Publication Date: 2007-02-27 PubMed ID: 17328936DOI: 10.1016/j.virol.2007.01.037Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The research article focuses on understanding the genetic variations and immune evasion strategies in equine infectious anemia virus (EIAV) during the inapparent stage of the disease, through a longitudinal study of the virus’s SU variation.
Research Methodology
- The researchers conducted a longitudinal study on a pony experimentally infected with the virulent EIAV(Wyo).
- They isolated viral RNA from the sample used for infection and from sequential serum samples from the pony.
- The isolated RNA was amplified using RT-PCR (Reverse transcription-polymerase chain reaction), cloned, and various clones were sequenced individually.
Study Findings
- The researchers succeeded in obtaining 147 SU clones from which they detected 71 distinct V3 variants.
- The variants were divided into five major non-overlapping groups (PND-1 to PND-5) which were associated with different stages of the clinical disease.
- They created chimeric viruses by inserting genotypes from each group into an infectious molecular clone. These chimeric viruses were then tested against neutralizing antibodies from different times after infection.
- They observed an overall increasing trend of resistance to neutralizing antibodies as the disease progressed.
- The PND genotype linked with the late stages of infection demonstrated resistance to both type-specific and broadly neutralizing antibodies. It also exhibited a reduced replication ability in lab conditions.
Conclusions
- The study concluded that neutralizing antibodies have a selective pressure throughout the infection. As the host’s immune response matures, the strategies of the virus for immune evasion and persistence evolve.
- The findings are crucial for understanding the complex interactions between EIAV and the horse immune system, and may help in the development of effective vaccines and treatments against EIAV.
Cite This Article
APA
Sponseller BA, Sparks WO, Wannemuehler Y, Li Y, Antons AK, Oaks JL, Carpenter S.
(2007).
Immune selection of equine infectious anemia virus env variants during the long-term inapparent stage of disease.
Virology, 363(1), 156-165.
https://doi.org/10.1016/j.virol.2007.01.037 Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA.
MeSH Terms
- Acute Disease
- Amino Acid Sequence
- Animals
- Carrier State / immunology
- Carrier State / virology
- Cell Line
- Chronic Disease
- Disease Progression
- Dogs
- Equine Infectious Anemia / immunology
- Equine Infectious Anemia / virology
- Evolution, Molecular
- Gene Products, env / genetics
- Gene Products, env / immunology
- Gene Products, env / metabolism
- Genetic Variation / immunology
- Genotype
- Horses
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / immunology
- Infectious Anemia Virus, Equine / physiology
- Molecular Sequence Data
- Neutralization Tests
- Selection, Genetic
- Time Factors
Grant Funding
- R01 CA128568 / NCI NIH HHS
- R21 CA097936 / NCI NIH HHS
- CA97936 / NCI NIH HHS
Citations
This article has been cited 16 times.- Gonzalez-Enriquez GV, Escoto-Delgadillo M, Vazquez-Valls E, Torres-Mendoza BM. SERINC as a Restriction Factor to Inhibit Viral Infectivity and the Interaction with HIV. J Immunol Res 2017;2017:1548905.
- Sponseller BA, Clark SK, Gilbertie J, Wong DM, Hepworth K, Wiechert S, Chandramani P, Sponseller BT, Alcott CJ, Bellaire B, Petersen AC, Jones DE. Macrophage effector responses of horses are influenced by expression of CD154. Vet Immunol Immunopathol 2016 Nov 1;180:40-44.
- Cervantes DT, Ball JM, Edwards J, Payne S. Horses naturally infected with EIAV harbor 2 distinct SU populations but are monophyletic with respect to IN. Virus Genes 2016 Feb;52(1):71-80.
- Schwartz EJ, Nanda S, Mealey RH. Antibody escape kinetics of equine infectious anemia virus infection of horses. J Virol 2015 Jul;89(13):6945-51.
- 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.
- 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.
- Wu W, Blythe DC, Loyd H, Mealey RH, Tallmadge RL, Dorman KS, Carpenter S. Decreased infectivity of a neutralization-resistant equine infectious anemia virus variant can be overcome by efficient cell-to-cell spread. J Virol 2011 Oct;85(19):10421-4.
- Taylor SD, Leib SR, Wu W, Nelson R, Carpenter S, Mealey RH. Protective effects of broadly neutralizing immunoglobulin against homologous and heterologous equine infectious anemia virus infection in horses with severe combined immunodeficiency. J Virol 2011 Jul;85(13):6814-8.
- 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.
- 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.
- Zielonka J, Bravo IG, Marino D, Conrad E, Perković M, Battenberg M, Cichutek K, Münk C. Restriction of equine infectious anemia virus by equine APOBEC3 cytidine deaminases. J Virol 2009 Aug;83(15):7547-59.
- Mealey RH, Leib SR, Littke MH, Wagner B, Horohov DW, McGuire TC. Viral load and clinical disease enhancement associated with a lentivirus cytotoxic T lymphocyte vaccine regimen. Vaccine 2009 Apr 21;27(18):2453-68.
- Bogerd HP, Tallmadge RL, Oaks JL, Carpenter S, Cullen BR. Equine infectious anemia virus resists the antiretroviral activity of equine APOBEC3 proteins through a packaging-independent mechanism. J Virol 2008 Dec;82(23):11889-901.
- Tallmadge RL, Brindley MA, Salmans J, Mealey RH, Maury W, Carpenter S. Development and characterization of an equine infectious anemia virus Env-pseudotyped reporter virus. Clin Vaccine Immunol 2008 Jul;15(7):1138-40.
- Sparks WO, Dorman KS, Liu S, Carpenter S. Naturally arising point mutations in non-essential domains of equine infectious anemia virus Rev alter Rev-dependent nuclear-export activity. J Gen Virol 2008 Apr;89(Pt 4):1043-1048.
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