The evolution of feline leukemia virus in vivo: A model of understanding viral genetic determinants of pathogenicity

Rohn, Jennifer Leigh.  University of Washington. ProQuest Dissertations Publishing, 1996. 0597183.

Abstract (summary)

Feline leukemia virus (FeLV) provides a valuable model for studying the retroviral determinants of pathogenicity because it causes multiple diseases in a natural outbred mammalian species, because it is characterized by genetic heterogeneity, and because previous studies have correlated specific disease outcome with particular viral mutations in cats infected with undefined virus populations. In this dissertation, I describe the isolation and characterization of viral variants that arose in cats that died with thymic lymphoma after experimental inoculation with molecularly cloned FeLV. This approach allowed correlation of the evolution and selection of specific viral mutations with disease progression. These studies showed that a spectrum of genetic alterations evolved during the course of infection in a number of cats. Four major classes of variants were detected: (1) Envelope genes with point mutations or deletions predicted to render the envelope protein defective were specifically prominent in tumors. (2) Variants with point mutations and duplications in the transcriptional control region of the long terminal repeat were isolated from tumor tissue. (3) Envelope genes with a unique insertion that bears resemblance to an immunodeficiency-inducing determinant were isolated from one cat tumor. One such variant gene was shown to confer onto an otherwise noncytopathic viral genome the phenotypes of enhanced replication, cytopathicity, and syncytium induction in feline T cells, and thus is predicted to be pathogenic in vivo. (4) Recombinant FeLV variants that had transduced a potential oncogene, feline Notch2, from the host cell genome were isolated from two cat tumors. Preliminary characterization showed that FeLV/Notch2 recombinant genomes could express a novel truncated Notch2 protein. This protein was targeted to the cell nucleus, possessed a structure similar to constitutively activated forms of Notch protein, and may have facilitated leukemogenicity by means of aberrant signaling in thymocytes. Taken together, the results described here add to our knowledge of the evolution and pathogenicity of retroviruses. Expanding upon these studies may ultimately further our understanding of the normal cellular processes that are subverted during infection.

Indexing (details)

0410: Microbiology
Identifier / keyword
Biological sciences; viral evolution
The evolution of feline leukemia virus in vivo: A model of understanding viral genetic determinants of pathogenicity
Rohn, Jennifer Leigh
Number of pages
Degree date
School code
DAI-B 57/07, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
Overbaugh, Julie M.
University of Washington
University location
United States -- Washington
Source type
Dissertation or Thesis
Document type
Dissertation/thesis number
ProQuest document ID
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL