DOI
https://doi.org/10.25772/7QM4-AH20
Defense Date
2006
Document Type
Thesis
Degree Name
Master of Science
Department
Microbiology & Immunology
First Advisor
Dr. Richard T. Marconi
Abstract
In North America, Borrelia burgdorferi is the primary causative agent of Lymedisease which is a growing health concern. The ability of B. burgdorferi to maintain chronic infection indicates that they are capable of immune evasion. A distinguishing characteristic of B. burgdorferi is the large number of sequences encoding predicted or known lipoproteins, including outer surface protein F (OspF). This study analyzes the specificity of the humoral immune response to B. burgdorferi B3 IMI OspF proteins during murine and human infection. Immunoblot analyses revealed a temporal expression of OspF proteins during infection and mapped the immunodominant epitopes which lie within the variable domains. To determine if OspF-related proteins are produced by other isolates, immunoblot analyses were performed using sera collected from mice and humans infected with diverse B. burgdorferi strains. Differences in the immunoreactivity profile to OspF proteins were seen among the infection sera tested. To identify the molecular basis of these differences, the ospF gene was isolated from several strains, sequenced and evolutionary analyses were conducted. These analyses revealed that OspF proteins show little diversity despite the separate geographic locations from which isolates originated. The high degree of OspF protein conservation seen in isolates from two distinct regions emphasizes the potential for OpsF proteins as vaccinogens or in serodiagnostic assays. Altogether, this study demonstrates the potential contribution of OspF proteins to immune evasion through its temporal expression during infection which may play specific roles at different stages of infection. Studies are underway to determine if inactivation of ospF genes through allelic exchange mutagenesis impacts on the pathogenicity of the Lyme disease spirochetes.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
June 2008