Bovine leukemia virus infection in cattle: Viral distribution and immunogenetic associations with disease progression
Mirsky, Michael L.
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https://hdl.handle.net/2142/22873
Description
Title
Bovine leukemia virus infection in cattle: Viral distribution and immunogenetic associations with disease progression
Author(s)
Mirsky, Michael L.
Issue Date
1995
Doctoral Committee Chair(s)
Lewin, Harris A.
Department of Study
Pathobiology
Discipline
Pathobiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Veterinary Science
Health Sciences, Immunology
Language
eng
Abstract
Bovine leukemia virus (BLV) was studied in naturally-infected cattle to clarify the cellular tropism of the virus at different stages of disease and obtain further evidence of a genetic basis for the development of BLV-associated disease. Flow cytometry was used to separate phenotypically defined subpopulations of 1-1000 cells into wells of 96-well plates, then the polymerase chain reaction (PCR) was employed to detect BLV provirus in each well. In five cows with and fourteen cows without persistent lymphocytosis (PL), BLV was found predominantly in CD5$\sp+$ and CD5$\sp-$ B-cells, with greater numbers of infected cells in the CD5$\sp+$ subset. Among non-PL cows the percentage of BLV-infected CD5$\sp+$ B-cells was correlated with total numbers of circulating lymphocytes. Among cows with PL there was 50- and 100-fold expansion of the infected CD5$\sp+$ and CD5$\sp-$ B-cell populations, respectively, without significant increases in uninfected B-cell numbers. We did not obtain convincing evidence that circulating monocytes or $\alpha$/$\beta$ T-cells contain BLV in cows with or without PL. To examine the relationship between major histocompatibility (Mhc) loci and development of disease, fourteen cows were paired on the basis of age and date of seroconversion without regard for lymphocyte count or PL status. One animal in each pair was selected for Mhc-associated resistance to PL and the other animal was selected for susceptibility to PL. PL-resistant cows had both fewer circulating CD5$\sp+$ B-cells and fewer infected CD5$\sp+$ and CD5$\sp-$ B-cells than did matched PL-susceptible cows. By reverse transcribing RNA prior to the PCR, we were able to detect the expression of the BLV tax gene in 0.01% of the circulating B-cells from a cow with PL, whereas $<$10$\sp{-5}$ B-cells expressed BLV env. These studies indicate that B-cells are the predominant target of BLV in vivo and strongly support a significant role for the Mhc in influencing the outcome of viral infection in vivo. The expression of CD5 by BLV-infected B-cells and the complete absence of viral mRNA in most of these cells with the development of PL are indicative of a unique mode of virus-mediated disease and may provide important clues into mechanisms of disease pathogenesis.
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