Date of Award
Doctor of Philosophy
Veterinary Microbiology and Preventive Medicine
Molecular, Cellular, and Developmental Biology; Neuroscience;
Lentiviruses are single-stranded RNA viruses generally associated with chronic diseases of the immune and central nervous systems. In contrast to the insidious, progressive nature of most lentiviral diseases, equine infectious anemia virus (EIAV) infection results in rapid onset of a variable disease course in equids. Acute disease is accompanied with high-titered viremia, thrombocytopenia, fever, depression, and inappetance. The chronic stage is usually characterized by recurrent episodes of disease. Equids that survive recurrent disease episodes progress to the inapparent stage of disease where no clinical signs are evident; however, there is persistent, ongoing virus replication. Lentiviruses exist within the host as a population of closely related genotypes, termed a quasispecies. Variation in the virus surface unit envelope glycoprotein (SU) has been demonstrated to contribute to immune evasion of host responses during chronic disease. However, little is known about the SU genotypes and phenotypes associated with disease progression to the inapparent stage of disease. The goal of this research is a genotypic and phenotypic characterization of the SU quasispecies during clinical and inapparent stages of disease. To accomplish this goal, I undertook a longitudinal study of SU variation in a pony experimentally inoculated with the virulent, wild-type, EIAVWyo. There was a marked increase in quasispecies diversity and divergence that coincided with maturation of the immune response and progression to the inapparent stage of disease. Variation was characterized by point mutations in each SU variable region as well as deletion/insertions within the principal neutralizing domain (PND). Genotypes representative of predominant PND variants were used to construct chimeric proviral clones for virus neutralization assays. A type-specific virus neutralizing antibody response was associated with resolution of acute disease. Variants predominant at later stages of disease showed increasing resistance to both type- and group-specific neutralizing antibody. Variants most resistant to group-specific antibody showed reduced replication fitness in vitro. These studies provide evidence that neutralizing antibody selects for resistant SU variants and thereby plays an important role in immune control of virus replication during the inapparent stage of disease.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu
Brett Alan Sponseller
Sponseller, Brett Alan, "Genetic and phenotypic variation of the equine infectious anemia virus surface unit envelope glycoprotein during disease progression " (2003). Retrospective Theses and Dissertations. 620.