The role of Variable Erythrocyte Surface Antigen (VESA1) proteins in Babesia bovi


Principal Investigator: KERRY SUE SONDGEROTH
Abstract: DESCRIPTION (provided by applicant): This proposal will investigate virulence mechanisms of cytoadherence/sequestration using Babesia bovis as a natural host model system. Virulent B. bovis infection is associated with development of severe clinical disease and neurological manifestations similar to those observed in human patients with severe malaria caused by virulent strains of P. falciparum. The proposed unique model enables in vivo study of virulence mechanisms using defined and reproducible virulence phenotypes. In this model, the role of cytoadhesion/sequestration in determining virulence and whether specific gene products mediate these phenotypes can be determined. Published and preliminary data from three virulent and derived attenuated B. bovis pairs strongly supports the role of VESA1 proteins in virulence, and the overall hypothesis that differential VESA1 protein expression alone may be responsible for mediating virulence. Clonal lines of virulent and attenuated strain pairs will be used and their differential phenotypes confirmed. The specific VESA1 surface protein dimer associated with sequestration and expressed by virulent versus attenuated strains both in vitro and in vivo will be identified using monoclonal antibodies. Direct demonstration that a specific VESA1 dimer is associated with sequestration and virulence will be determined by complementation and expression of cytoadhesion and virulence associated ves1 gene(s) in the attenuated T2Bo clonal line, followed by an in vivo study to demonstrate acquisition of the virulence phenotype. If the hypothesis is correct, and if similar mechanisms are used in other pathogens, molecular targets for intervention to prevent severe clinical manifestations and death associated with hemoparasite infection can be further examined. Future directions will be to determine specific domain(s) of VESA1 proteins required for virulence, determine whether these domains are present in other VESA1 proteins and if so whether these proteins are also associated with virulence. Once this is established, the design and testing of virulence directed interventions such as peptide analogues or vaccines to reduce the morbidity and mortality associated with hemoparasite infection in animals and humans will be possible.
Funding Period: 2011-08-15 - 2016-06-30
more information: NIH RePORT

Top Publications

  1. ncbi Acute and persistent infection by a transfected Mo7 strain of Babesia bovis
    Carlos E Suarez
    Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164 704, United States
    Mol Biochem Parasitol 185:52-7. 2012

Detail Information


  1. ncbi Acute and persistent infection by a transfected Mo7 strain of Babesia bovis
    Carlos E Suarez
    Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164 704, United States
    Mol Biochem Parasitol 185:52-7. 2012
    ..Together, the data demonstrates that exogenous B. bovis transgenes can be expressed and remain stable throughout acute and persistent infection in calves...

Research Grants30

  1. Chemokines in Zambian children with Cerebral Malaria
    Monique F Stins; Fiscal Year: 2013
  2. Molecular pathogenesis and genetic diversification of childhood falciparum malari
    STEVE MYER TAYLOR; Fiscal Year: 2013
    ..abstract_text> ..
  3. Rocky Mountain Regional Center of Excellence or Biodefense and Emerging Infectiou
    John T Belisle; Fiscal Year: 2013
    ..abstract_text> ..
  4. Characterize functions of T. brucei RAP1 and TRF in antigenic variation and telom
    Bibo Li; Fiscal Year: 2013
    ..Identification of novel factors involved in antigenic variation also provides more potential targets for anti-parasite drugs and helps for eventual elimination of this parasite. ..
  5. Pacific NorthWest Regional Center of Excellence (PNWRCE)
    Jay A Nelson; Fiscal Year: 2013
    ..pseudomallei host pathogen response during both the septicemic as well as the intracellular phases of the disease. ..
  6. Southeast Regional Centers of Excellence for Biodefense &Emerging Infectious Di
    Philip Frederick Sparling; Fiscal Year: 2013
    ..SERCEB brings new investigators to the biodefense effort through a combination of educational programs, support of innovative new projects, and the synergistic interactions among its world-class investigators. ..
  7. New England Regional Center of Excellence in Biodefense and Emerging Infectious D
    Dennis L Kasper; Fiscal Year: 2013
    ..NERCE will also continue its Developmental Projects program and Career Development in Biodefense program in an effort to initiate new research efforts and to attract new investigators to this field. ..
  8. Northeast Biodefense Center
    W Ian Lipkin; Fiscal Year: 2013
    ..As a Center based in a School of Public Health and a State Department of Health, the NBC has a firm commitment to and practical understanding of Emergency Preparedness. ..
  9. The effect of peptide therapy and allergen provocation on Fel d1-specific T Cells
    Mark Larché; Fiscal Year: 2013
    ..Additionally this Aim will assess the effects of peptide immunotherapy in the murine allergen challenge model ..
  10. Pacific Southwest RCE for Biodefense &Emerging Infectious Diseases Research
    Alan G Barbour; Fiscal Year: 2013
    ..abstract_text> ..
  11. Cerebral Malaria: Mechanisms of disease and neurological salvage
    Mahalia S Desruisseaux; Fiscal Year: 2013
    ..Thus, vascular compromise and alterations in Akt and tau may be important in the pathogenesis of malaria and may provide rational targets of drug therapy to ameliorate the consequences of this infection. ..
  12. Platelet Mediated Immune Responses in Experimental Cerebral Malaria
    Angela A Aggrey; Fiscal Year: 2013
    ..abstract_text> ..
  13. Alternative Approaches for E. faecalis Infections
    Barbara E Murray; Fiscal Year: 2013
    ..We seek to understand how these bacteria attach to heart valves and other human tissues and proteins, and to develop ways to prevent these infections. ..