BOVINE LEUKOSIS VIRUS PATHOGENESIS

Project: Research project

Project Details

Description

The long term goal of this project is to define the mechanism(s)
of bovine leukosis virus (BLV) pathogenesis in cattle as an animal
model for human retrovirus-associated lymphoid malignancies. Our
working hypothesis is that BLV-infected T lymphocytes are pivotal
to the abnormal lymphoproliferation. This hypothesis will be
tested by extensive characterization of the tropism of BLV for
mononuclear leukocyte subpopulations and associated molecular
events that lead to lymphocytosis and/or tumor development. Cell
subpopulations from all major lymphoid compartments will be
analyzed from animals at multiple stages of disease progression
(aleukemic, lymphocytotic & tumor-bearing stages). Mononuclear
leukocyte subpopulation perturbations will be identified by flow
cytometry and immunohistology. Viral tropism for mononuclear
subpopulations will be determined by identification of cells
harboring provirus (Southern hybridization & PCR). The ability of
such cells to express BLV proteins will be determined by
immunofluorescence staining of intracellular antigen (flow
cytometry & immunohistology); evidence of cellular expression of
BLV proteins with potential cell-growth regulatory activity
(specifically the trans-activating protein, tax) will be by
Northern hybridization- and/or PCR-based identification of mRNA.
The genetic clonality of T and B. cells will be by identification
of Ig and TCR gene rearrangement. A role for BLV tax-driven T
lymphocyte production of B and/or T cell growth factor(s) will be
determined by functional assays as well as Northern hybridization-
and/or PCR-based identification of interleukin mRNA. Association
of all data obtained, with the state of disease progression, will
greatly increase our understanding of BLV pathogenesis and provide
additional insight, at the cellular and molecular level, into
retrovirus-mediated dysregulation of lymphocyte proliferation.
StatusFinished
Effective start/end date5/13/934/30/96

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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