Degree Type

Dissertation

Date of Award

1999

Degree Name

Doctor of Philosophy

Department

Theses & dissertations (Interdisciplinary)

Major

Microbiology

First Advisor

Susan Carpenter

Second Advisor

F. Chris Minion

Abstract

Members of the lentivirus subfamily of retroviruses are characterized as causing slow, chronic disease. Atypical of other lentiviruses, such as human immunodeficiency virus type 1, equine infectious anemia virus (EIAV) may produce a rapid, variable disease course in horses. Infected horses may undergo an, acute episode of disease involving viremia, fever, and thrombocytopenia. Following this acute period, horses may resolve to an inapparent infection or suffer a chronic period of additional cycles of viremia, fever, and thrombocytopenia. Horses which survive clinical episodes usually become inapparent carriers of the virus for life. Numerous virus and host factors contribute to the phenotypic manifestations of disease. These include, but are not limited to, the rate of virus replication, the host immune response, and genetic variation of the virus. Genetic variation in EIAV has been identified in a region overlapped by the genes encoding the transmembrane protein and the trans-regulatory protein Rev. Rev is a nucleocytoplasmic transport protein which regulates the expression of viral structural proteins and progeny RNA molecules during the late phase of virus replication. Therefore, factors which modulate Rev activity may result in changes in virus replication and ultimately contribute to virus pathogenesis in vivo. The long term goal of this research project is to determine the contribution of Rev variation to the manifestation of clinical disease during an EIAV infection. To accomplish this goal, we first determined that genetic variation in Rev can modulate the rate of virus replication in vitro;We then characterized variation within Rev in an experimentally-infected pony. Functional analysis of the dominant Rev variants at various time points during infection indicated that the variants dominant during the clinical periods possessed more nuclear export activity than those dominant in the acute or aclinical periods. To further understand the significance of Rev variation, we also mapped the cis- and trans-acting elements required for the nuclear export and alternative splicing activities of Rev. Specifically, we mapped the alternative splicing domain of Rev and identified the RRE of EIAV. These studies provide strong evidence that variation in Rev contributes to clinical disease during the course of an EIAV infection.

DOI

https://doi.org/10.31274/rtd-180813-13712

Publisher

Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/

Copyright Owner

Michael Andrew Belshan

Language

en

Proquest ID

AAI9950079

File Format

application/pdf

File Size

128 pages

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