Abstract
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.
Highlights
Arthropod-borne, pathogenic spirochetes of the genus Borrelia adjust expression of their genes for the particular host of the moment [1]
We provide additional evidence that Variable Tick Protein (Vtp) is expressed in mammals as well as in ticks and that specific anti-Vtp antibodies are elicited during infection of the mouse
As reported by Marcsisin et al [33], mice were immunized with viable cells of the variable membrane proteins” (VMP)-less vtpFS83 mutant of strain HS1, and the post-boost sera were used in microagglutination and western blot assays
Summary
Arthropod-borne, pathogenic spirochetes of the genus Borrelia adjust expression of their genes for the particular host of the moment [1]. Borrelia burgdorferi, a cause of Lyme disease, abundantly expresses the OspA surface protein in the unfed tick, but down-regulates expression with the entry of blood into the vector’s intestine, and this reduction continues after transmission into a vertebrate host (reviewed in [2]). As befits a protein that is primarily expressed in an invertebrate with a limited immune system [3], there are few differences between the OspA proteins of different strains of the species [4, 5]. The limited inter-strain diversity of OspA contrasts with the marked diversity of OspC proteins [5, 7], which commonly elicit antibodies in natural vertebrate hosts [8] and appear to be under selection by adaptive immunity [9]
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