Rickettsia are obligate intracellular bacteria that can cause anemia, leukopenia, thrombocytopenia, or vasculitis depending on the host cell infected. In animals that survive acute infection, many rickettsia establish lifelong persistent infection in the face of high antibody titers and T lymphocyte responsiveness that mediate resistance to challenge with the initial infecting strain. How rickettsia persist despite an effective immune response is unknown. Importantly, persistently infected animals provide a reservoir for arthropod-borne transmission of rickettsia to additional susceptible hosts. A. marginale is an intraerythrocytic rickettsia of cattle in which infection persists for the life of the animal. During persistent A. marginale infection, cyclic rickettsemia in the face of an effective immune response suggests the emergence of antigenic variants. Genomic and antigenic diversity is evident in the multigene family encoding the A. marginale major surface protein 2 (MSP-2), a putative adhesin for erythrocyte binding that has been shown to be an important target for immune responses during control of acute rickettsemia. The proposed project tests the hypothesis that MSP-2 antigenic variants emerge during rickettsemic cycles in persistent A. marginale infection. Identifying molecules that vary during persistent infection can then direct research towards molecular mechanisms of antigenic variation. Determining mechanisms of persistence in A. marginale infection may direct new approaches for controlling persistence and transmission of A. marginale and other rickettsia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI001371-02
Application #
2429344
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Project Start
1996-06-01
Project End
1999-05-31
Budget Start
1997-06-01
Budget End
1998-05-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Washington State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164
Rurangirwa, F R; Stiller, D; French, D M et al. (1999) Restriction of major surface protein 2 (MSP2) variants during tick transmission of the ehrlichia Anaplasma marginale. Proc Natl Acad Sci U S A 96:3171-6
French, D M; Brown, W C; Palmer, G H (1999) Emergence of Anaplasma marginale antigenic variants during persistent rickettsemia. Infect Immun 67:5834-40
French, D M; McElwain, T F; McGuire, T C et al. (1998) Expression of Anaplasma marginale major surface protein 2 variants during persistent cyclic rickettsemia. Infect Immun 66:1200-7
Palmer, G H; Abbott, J R; French, D M et al. (1998) Persistence of Anaplasma ovis infection and conservation of the msp-2 and msp-3 multigene families within the genus Anaplasma. Infect Immun 66:6035-9