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Published on: October 23, 2013
Emergence of Anaplasma marginale antigenic variants during persistent rickettsemia
D M French1, W C Brown, G H Palmer
1Program in Vector-Borne Diseases, Department of Veterinary Microbiology, Washington State University, Pullman, Washington 99164-7040, USA.
Abstract:
Anaplasma marginale is an ehrlichial pathogen of cattle, in the order Rickettsiales, that establishes persistent cyclic rickettsemia in the infected host. Within each rickettsemic cycle, A. marginale expressing antigenically variant major surface protein 2 (MSP2) emerge. By cloning 17 full-length msp2 transcripts expressed during cyclic rickettsemia, we determined that emergent variants have a single, central hypervariable region encoding variant B-cell epitopes. The N- and C-terminal regions are highly conserved among the expressed A. marginale variants, and similar sequences define the MSP2 homologues in the agent of human granulocytic ehrlichiosis (HGE). This is in contrast to the MSP2 homologues in ehrlichial genogroup I pathogens, Ehrlichia chaffeensis, Ehrlichia canis, and Cowdria ruminantium, that have multiple hypervariable regions. By defining the variable and conserved regions, we were able to show that the single hypervariable region of A. marginale MSP2 encodes epitopes that are immunogenic and induce variant-specific antibody responses during persistent infection. These findings demonstrate that the MSP2 structural variants that emerge during each cycle of persistent rickettsemia are true antigenic variants, consistent with MSP2 antigenic variation as a mechanism of A. marginale persistence.
Insights
Anaplasma marginale causes persistent cattle infections by varying its Major Surface Protein 2 (MSP2). This variation, driven by a single hypervariable region, allows the pathogen to evade the host immune response during rickettsemic cycles.
Area of Science:
- Veterinary Microbiology
- Immunology
- Molecular Biology
Background:
- Anaplasma marginale, an ehrlichial pathogen, causes cyclic rickettsemia in cattle.
- During infection, A. marginale exhibits antigenic variation in its Major Surface Protein 2 (MSP2).
Purpose of the Study:
- To investigate the structural basis of MSP2 antigenic variation in Anaplasma marginale.
- To determine the role of MSP2 variation in the persistence of A. marginale infections.
Main Methods:
- Cloning and sequencing of 17 full-length msp2 transcripts from cyclic rickettsemic cattle.
- Comparative sequence analysis of MSP2 homologues across different ehrlichial species.
Main Results:
- Emergent A. marginale variants possess a single, central hypervariable region in MSP2, encoding variant B-cell epitopes.
- N- and C-terminal regions of MSP2 are conserved among A. marginale variants and similar to MSP2 homologues in the agent of human granulocytic ehrlichiosis.
- Unlike other ehrlichial genogroup I pathogens, A. marginale MSP2 has a single hypervariable region.
- The hypervariable region of MSP2 elicits immunogenic, variant-specific antibody responses during persistent infection.
Conclusions:
- The single hypervariable region of A. marginale MSP2 is responsible for antigenic variation.
- MSP2 antigenic variation is a key mechanism enabling Anaplasma marginale persistence in cattle.
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