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Development and Characterization of Early Immunological Events of a Rabbit Model of Milk-Borne Transmission of Human T-Lymphotropic Virus Type 1 Infection

Haines, Robyn A.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1337181159

Abstract Details

2012, Doctor of Philosophy, Ohio State University, Comparative and Veterinary Medicine.
The complex retrovirus Human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma and other lymphocyte-mediated inflammatory disorders. In endemic regions, HTLV-1 is primarily spread from mother to child through infected breast milk. The establishment of persistent HTLV-1 infection following the ingestion of infected lymphocytes is determined by the delicate balance between viral spread and the host immune response. The immunopathogenesis of these early events is not completely understood, and advances in this area have been hindered by the lack of an appropriate animal model. This thesis describes a novel rabbit model of HTLV-1 milk-borne infections, and provides data to understand the early immunological and virological events following oral mucosal exposure to HTLV-1. Herein, we performed an extensive examination of the rabbit gut-associated lymphoid tissue. Using two quantitative methods to exam lymphocyte subsets within the major inductive sites our data revealed similarities between rabbits and humans. This information validates this species as a model for mucosal immunology studies following oral exposure to HTLV-1 and establishes reference ranges for future studies. Our data provides important knowledge of the immune response against HTLV-1 infection following oral exposure to infected lymphocytes. We established a protocol for infection via the oral mucosal route using a method that mimics infant exposure to repeated doses of comparable numbers of infected lymphocytes. We further characterized this model of infection through evaluation of humoral and cellular immune responses and viral parameters. We determined that rabbits exposed orally to HTLV-1 infected lymphocytes develop a persistent infection characterized by a delayed and variable humoral immune response similar to infected infants. Rabbits exposed by this route also displayed a variable, decreased and delayed peripheral cellular immune response with lower and variable proviral loads and p19 antigen production from ex vivo cultured peripheral blood mononuclear cells when compared to rabbits infected by the intravenous route. This animal model of HTLV-1 infection was used to study early spatial and temporal events following mucosal viral infection. Our data indicates that oral inoculation with HTLV-1 infected lymphocytes results in systemic virus distribution by four weeks post inoculation. Early viral reservoirs include the spleen, mesenteric lymph node, and gut-associated lymphoid tissues (GALT). Within the GALT, there is quiescent integrated provirus within the effector sites and mesenteric lymph node, and actively replicating virus within the inductive sites and spleen. Collectively, data presented in this thesis indicates that HTLV-1 infection following oral exposure induces a delayed and decreased systemic immune response to viral exposure. Our data indicates that the events associated with development of HTLV-1 persistent infections following milk-borne transmission occur below the level of detection within tissue compartments for the first four weeks following exposure, prior to systemic spread.
Stefan Neiweisk, DVM/PhD (Advisor)
Michael Lairmore, DVM/PhD (Committee Member)
Burkhard Mary Jo, DVM/PhD (Committee Member)
Wellman Maxey, DVM/PhD (Committee Member)
247 p.
Immunology; Virology
HTLV-1; Rabbit; Mother to child transmission; Oral transmission, Mucosal Immunology

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Citations

  • Haines, R. A. (2012). Development and Characterization of Early Immunological Events of a Rabbit Model of Milk-Borne Transmission of Human T-Lymphotropic Virus Type 1 Infection [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1337181159

    APA Style (7th edition)

  • Haines, Robyn. Development and Characterization of Early Immunological Events of a Rabbit Model of Milk-Borne Transmission of Human T-Lymphotropic Virus Type 1 Infection. 2012. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1337181159.

    MLA Style (8th edition)

  • Haines, Robyn. "Development and Characterization of Early Immunological Events of a Rabbit Model of Milk-Borne Transmission of Human T-Lymphotropic Virus Type 1 Infection." Doctoral dissertation, Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1337181159

    Chicago Manual of Style (17th edition)

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© 2012, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.