Diversity of Babesia bovis merozoite surface antigen genes in the Philippines

ABSTRACT A hypervariable region (HVR) previously identified in the carboxy-terminal one-third of the Babesia bovis variable merozoite surface antigen family was more extensively analyzed in merozoite surface antigen 1 (MSA-1) from 16 strains and isolates. The MSA-1 HVR is proline rich and contains three semiconserved motifs nearly identical to those described for the related family member MSA-2. Two MSA-1-specific monoclonal antibodies previously shown to be reactive with the merozoite surface bound to a recombinant construct encoding the HVR, indicating that the HVR is surface exposed and accessible to antibody binding. Importantly, these surface-reactive, HVR-specific monoclonal antibodies were capable of inhibiting merozoite infectivity of the host erythrocyte in vivo. The results indicate that the MSA-1 HVR is involved in erythrocyte invasion and suggest that selection of MSA-1 variants may be driven by invasion-blocking antibodies.

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Persistence of Antibodies against Epitopes Encoded by a Single Gene Copy of the Babesia bovis Merozoite Surface Antigen 1 (MSA-1)

Journal of Parasitology ◽

10.2307/3284511 ◽

1998 ◽

Vol 84 (2) ◽

pp. 449 ◽

Cited By ~ 3

Author(s):

Terry F. McElwain ◽

Stephen A. Hines ◽

Guy H. Palmer

Keyword(s):

Surface Antigen ◽

Single Gene ◽

Babesia Bovis ◽

Gene Copy ◽

Merozoite Surface Antigen

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

Infection and Immunity ◽

10.1128/iai.73.11.7180-7189.2005 ◽

2005 ◽

Vol 73 (11) ◽

pp. 7180-7189 ◽

Cited By ~ 48

Author(s):

Shawn J. Berens ◽

Kelly A. Brayton ◽

John B. Molloy ◽

Russell E. Bock ◽

Ala E. Lew ◽

...

Keyword(s):

Surface Antigen ◽

Protective Immunity ◽

Sequence Variation ◽

Immune Escape ◽

Hypervariable Region ◽

Babesia Bovis ◽

Erythrocyte Invasion ◽

Merozoite Surface Antigen ◽

Nucleotide Repeats ◽

Degenerate Nucleotide

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.

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Surface epitope localization and gene structure of a Babesia bovis 44-kilodalton variable merozoite surface antigen

Molecular and Biochemical Parasitology ◽

10.1016/0166-6851(92)90128-7 ◽

1992 ◽

Vol 55 (1-2) ◽

pp. 75-84 ◽

Cited By ~ 39

Author(s):

Douglas P. Jasmer ◽

David W. Reduker ◽

Stephen A. Hines ◽

Lance E. Perryman ◽

Travis C. McGuire

Keyword(s):

Surface Antigen ◽

Gene Structure ◽

Babesia Bovis ◽

Merozoite Surface Antigen

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Sequence Variation and Immunologic Cross-Reactivity among Babesia bovis Merozoite Surface Antigen 1 Proteins from Vaccine Strains and Vaccine Breakthrough Isolates

Infection and Immunity ◽

10.1128/iai.73.9.5388-5394.2005 ◽

2005 ◽

Vol 73 (9) ◽

pp. 5388-5394 ◽

Cited By ~ 36

Author(s):

Tanya LeRoith ◽

Kelly A. Brayton ◽

John B. Molloy ◽

Russell E. Bock ◽

Stephen A. Hines ◽

...

Keyword(s):

Vaccine Strain ◽

Surface Antigen ◽

Sequence Variation ◽

Antigenic Variation ◽

Cross Reactivity ◽

Babesia Bovis ◽

Extracellular Region ◽

Merozoite Surface Antigen ◽

The Difference ◽

Blocking Antibodies

ABSTRACT The Babesia bovis merozoite surface antigen 1 (MSA-1) is an immunodominant membrane glycoprotein that is the target of invasion-blocking antibodies. While antigenic variation has been demonstrated in MSA-1 among strains from distinct geographical areas, the extent of sequence variation within a region where it is endemic and the effect of variation on immunologic cross-reactivity have not been assessed. In this study, sequencing of MSA-1 from two Australian B. bovis vaccine strains and 14 breakthrough isolates from vaccinated animals demonstrated low sequence identity in the extracellular region of the molecule, ranging from 19.8 to 46.7% between the T vaccine strain and eight T vaccine breakthrough isolates, and from 18.7 to 99% between the K vaccine strain and six K vaccine breakthrough isolates. Although MSA-1 amino acid sequence varied substantially among strains, overall predicted regions of hydrophilicity and hydrophobicity in the extracellular domain were conserved in all strains examined, suggesting a conserved functional role for MSA-1 despite sequence polymorphism. Importantly, the antigenic variation created by sequence differences resulted in a lack of immunologic cross-reactivity among outbreak strains using sera from animals infected with the B. bovis vaccine strains. Additionally, sera from cattle hyperinfected with the Mexico strain of B. bovis and shown to be clinically immune did not cross-react with MSA-1 from any other isolate tested. The results indicate that isolates of B. bovis capable of evading vaccine-induced immunity contain an msa-1 gene that is significantly different from the msa-1 of the vaccine strain, and that the difference can result in a complete lack of cross-reactivity between MSA-1 from vaccine and breakthrough strains in immunized animals.

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Genetic variations in merozoite surface antigen genes of Babesia bovis detected in Vietnamese cattle and water buffaloes

Infection Genetics and Evolution ◽

10.1016/j.meegid.2014.12.035 ◽

2015 ◽

Vol 30 ◽

pp. 288-295 ◽

Cited By ~ 10

Author(s):

Naoaki Yokoyama ◽

Thillaiampalam Sivakumar ◽

Bumduuren Tuvshintulga ◽

Kyoko Hayashida ◽

Ikuo Igarashi ◽

...

Keyword(s):

Surface Antigen ◽

Genetic Variations ◽

Babesia Bovis ◽

Water Buffaloes ◽

Merozoite Surface Antigen

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The Babesia bovis Merozoite Surface Antigen 2 Locus Contains Four Tandemly Arranged and Expressed Genes Encoding Immunologically Distinct Proteins

Infection and Immunity ◽

10.1128/iai.70.7.3566-3575.2002 ◽

2002 ◽

Vol 70 (7) ◽

pp. 3566-3575 ◽

Cited By ~ 67

Author(s):

Monica Florin-Christensen ◽

Carlos E. Suarez ◽

Stephen A. Hines ◽

Guy H. Palmer ◽

Wendy C. Brown ◽

...

Keyword(s):

Amino Acid ◽

B Cell ◽

Surface Antigen ◽

Cell Epitope ◽

Amino Acid Identity ◽

Immune Serum ◽

Surface Proteins ◽

Babesia Bovis ◽

Genomic Locus ◽

Merozoite Surface Antigen

ABSTRACT Members of the variable merozoite surface antigen (vmsa) gene family of Babesia bovis encode membrane proteins involved in erythrocyte invasion. In this study, we have identified and sequenced the complete 8.3-kb genomic locus containing msa-2, a member of the vmsa family, in the biologically cloned Mexico Mo7 strain. Four tandemly arranged copies of msa-2-related genes were found in the locus. The four genes, designated msa-2a1 (which corresponds to the originally described msa-2 gene), msa-2a2 , msa-2b, and msa-2c, were shown to be transcribed and expressed and encode proteins with open reading frames ranging in size from 266 (MSA-2c) to 317 (MSA-2a1) amino acids. MSA-2a1 and -2a2 are the most closely related of the four proteins (90% identity), differing by (i) the number of 24-amino-acid repeats that comprise a surface-exposed B-cell epitope and (ii) the presence of a 32-amino-acid area of recombination between MSA-2a2 and -2b. In contrast, msa-2c is most closely related to the previously described babr 0.8 gene in Australia strains of B. bovis. Comparison of MSA-2 proteins in the Argentina R1A strain of B. bovis with the Mexico Mo7 clone revealed a relatively high degree of conservation (83.6, 69.4, 79.1, and 88.7% amino acid identity for MSA-2a1, -2a2, -2b, and -2c, respectively), in contrast to the extensive MSA-1 sequence variation (52% identity) between the same two strains. Postinfection bovine immune serum contains antibodies that bound to each of the recombinant MSA-2 proteins. Blocking assays demonstrated the presence of unique B-cell epitopes in MSA-2a1, -2b, and -2c. The results support the evolution of the msa-2 locus through at least two gene duplications, with selection for multiple related but antigenically distinct merozoite surface proteins.

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