Expression of the Tick-Associated Vtp Protein of Borrelia hermsii in a Murine Model of Relapsing Fever

Borrelia hermsii, a spirochete and cause of relapsing fever, is notable for its immune evasion by multiphasic antigenic variation within its vertebrate host. This is based on a diverse repertoire of surface antigen genes, only one of which is expressed at a time. Another major surface protein, the Variable Tick Protein (Vtp), is expressed in the tick vector and is invariable at its genetic locus. Given the limited immune systems of ticks, the finding of considerable diversity among the Vtp proteins of different strains of B. hermsii was unexpected. We investigated one explanation for this diversity of Vtp proteins, namely expression of the protein in mammals and a consequent elicitation of a specific immune response. Mice were infected with B. hermsii of either the HS1 or CC1 strain, which have antigenically distinctive Vtp proteins but otherwise have similar repertoires of the variable surface antigens. Subsequently collected sera were examined for antibody reactivities against Vtp and other antigens using Western blot analysis, dot blot, and protein microarray. Week-6 sera of infected mice contained antibodies that were largely specific for the Vtp of the infecting strain and were not attributable to antibody cross-reactivities. The antibody responses of the mice infected with different strains were otherwise similar. Further evidence of in vivo expression of the vtp gene was from enumeration of cDNA sequence reads that mapped to a set of selected B. hermsii genes. This measure of transcription of the infecting strain’s vtp gene was ~10% of that for the abundantly-expressed, serotype-defining variable antigen gene but similar to that of genes known for in vivo expression. The findings of Vtp expression in a vertebrate host and elicitation of a specific anti-Vtp antibody response support the view that balancing selection by host adaptive immunity accounts in part for the observed diversity of Vtp proteins.