title: Merozoite surface antigen 2 proteins of Babesia bovis vaccine breakthrough isolates contain a unique hypervariable region composed of degenerate repeats.
abstract: The merozoite surface antigen 2 (MSA-2) proteins of Babesia bovis are members of the variable merozoite surface antigen (VMSA) family that have been implicated in erythrocyte invasion and are important targets for antibody-mediated blocking of invasion. Extensive sequence variation in another VMSA member, MSA-1, has been shown in all vaccine breakthrough isolates. To test the hypothesis that the msa-2 genes of vaccine breakthrough isolates would also encode a diverse set of proteins, the complete msa-2 locus was characterized from 12 Australian B. bovis strains and isolates, including two vaccine strains and eight vaccine breakthrough isolates, and compared to the loci in previously and newly characterized American strains. In contrast to American strains, the msa-2 loci of all Australian strains and isolates examined contain, in addition to msa-2c, only a solitary gene (designated msa-2a/b) closely related to American strain msa-2a and msa-2b. Nevertheless, the proteins encoded by these genes are quite diverse both between and within geographic regions and harbor evidence of genetic exchange among other VMSA family members, including msa-1. Moreover, all but one of the Australian breakthrough isolate MSA-2a/b proteins is markedly different from the vaccine strain from which immune escape occurred, consistent with their role in strain-specific protective immunity. The densest distribution of polymorphisms occurs in a hypervariable region (HVR) within the carboxy third of the molecule that is highly proline rich. Variation in length and content of the HVR is primarily attributable to differences in the order and number of degenerate nucleotide repeats encoding three motifs of unknown function.
authors.affiliation: Program in Vector-Borne Diseases, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA. sberens@vetmed.wsu.edu
authors.forename: Shawn J
authors.initials: SJ
authors.lastname: Berens
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Brayton
authors.forename: John B
authors.initials: JB
authors.lastname: Molloy
authors.forename: Russell E
authors.initials: RE
authors.lastname: Bock
authors.forename: Ala E
authors.initials: AE
authors.lastname: Lew
authors.forename: Terry F
authors.initials: TF
authors.lastname: McElwain
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D016793:Babesia bovis / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D014644:Genetic Variation; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016052:Protozoan Vaccines / Q000276:immunology*; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid
chemical_list: D000953:Antigens, Protozoan; D008565:Membrane Proteins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines