The long range objective of the proposed study is to gain insight into the pathogenetic mechanisms of Bartonella species during opportunistic infection of patients co-infected with HIV. Bartonella syndromes in HIV-infected patients include severe, even fatal infections such as bacillary angiomatosis, peliosis hepatitis, relapsing bacteremia, endocarditis, cat scratch disease, neuroretinitis and encephalopathy. From clinical observations, there are two striking manifestations of Bartonella pathogenesis: relapsing and persistent bloodstream infections and vascular proliferative lesions, yet nothing is known about the bacterial pathogenetic mechanisms involved in either, largely because no animal models exist. the immediate objective of these studies is to study the mechanisms of Bartonella pathogenesis by developing an animal model, and utilizing this animal model to characterize the host response to infection and mechanisms of virulence gene expression associated with B. henselae and B. quintana. The applicant's first goal is to develop an animal model for AIDS-associated opportunistic Bartonella infections in by infecting animals with B. henselae or B. quintana, with the goal of inducing one or both endpoint disease manifestations: persistent bloodstream infection and angiogenic lesions. The second goal is to utilize the model to study Bartonella pathogenesis (course of infection, pathological changes, humoral immune response). Through development of an animal model and subsequent study of the disease course, pathological manifestations and mammalian host-bacterium interactions, the applicants hope to gain insight into the basis for Bartonella pathogenesis including host immune response and persistent and relapsing infection, which will ultimately lead to improved diagnosis, treatment and prevention of Bartonella infection in HIV-infected patients.
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