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Infection and Immunity, November 2005, p. 7180-7189, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7180-7189.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Merozoite Surface Antigen 2 Proteins of Babesia bovis Vaccine Breakthrough Isolates Contain a Unique Hypervariable Region Composed of Degenerate Repeats

Shawn J. Berens,1* Kelly A. Brayton,1 John B. Molloy,2 Russell E. Bock,3 Ala E. Lew,2 and Terry F. McElwain1

Program in Vector-Borne Diseases, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164-7040,1 Emerging Technologies/Delivery, Queensland Department of Primary Industries and Fisheries, c/o Locked Mail Bag No. 4, Moorooka 4105, Queensland, Australia,2 Tick Fever Centre, Biosecurity, Queensland Department of Primary Industries and Fisheries, 280 Grindle Road, Wacol, Queensland, Australia3

Received 1 July 2005/ Returned for modification 12 August 2005/ Accepted 20 August 2005

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.

* Corresponding author. Mailing address: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040. Phone: (509) 335-6346. Fax: (509) 335-8529. E-mail: sberens{at}vetmed.wsu.edu.

Editor: W. A. Petri, Jr.

Infection and Immunity, November 2005, p. 7180-7189, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7180-7189.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Berens, S. J., Brayton, K. A., McElwain, T. F. (2007). Coinfection with Antigenically and Genetically Distinct Virulent Strains of Babesia bovis Is Maintained through All Phases of the Parasite Life Cycle. Infect. Immun. 75: 5769-5776 [Abstract] [Full Text]  
  • LeRoith, T., Berens, S. J., Brayton, K. A., Hines, S. A., Brown, W. C., Norimine, J., McElwain, T. F. (2006). The Babesia bovis Merozoite Surface Antigen 1 Hypervariable Region Induces Surface-Reactive Antibodies That Block Merozoite Invasion.. Infect. Immun. 74: 3663-3667 [Abstract] [Full Text]  


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