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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.
Infection and Immunity
|October 26, 1999
Summary
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.