Immune selection of equine infectious anemia virus env variants during the long-term inapparent stage of disease.

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TitleImmune selection of equine infectious anemia virus env variants during the long-term inapparent stage of disease.
Publication TypeJournal Article
Year of Publication2007
AuthorsSponseller, BA, Sparks, WO, Wannemuehler, Y, Li, Y, Antons, AK, J Oaks, L, Carpenter, S
JournalVirology
Volume363
Issue1
Pagination156-65
Date Published2007 Jun 20
ISSN0042-6822
KeywordsAcute Disease, Amino Acid Sequence, Animals, Carrier State, Cell Line, Chronic Disease, Disease Progression, Dogs, Equine Infectious Anemia, Evolution, Molecular, Gene Products, env, Genetic Variation, Genotype, Horses, Infectious Anemia Virus, Equine, Molecular Sequence Data, Neutralization Tests, Selection, Genetic, Time Factors
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.

DOI10.1016/j.virol.2007.01.037
Alternate JournalVirology
PubMed ID17328936
Grant ListCA97936 / CA / NCI NIH HHS / United States
R21 CA097936 / CA / NCI NIH HHS / United States