Abstract

Retroviruses are capable of inducing ablative as well as proliferative diseases of the lymphoreticular system. Induction of T-cell leukemia/lymphoma is associated in cats with infection with subgroups A and B Feline Leukemia Viruses (FeLV), and in humans with infection with Type I Human T-cell Lymphotrophic Viruses (HTLV-I). In contrast, subgroup C FeLVs will induce aplastic anemia in cats, and HTLV-III is the probable cause of AIDS in humans. Because the spectrum of disease induced by FeLV and HTLV is so similar, FeLV is considered to be the most appropriate animal model for virus-associated human malignancy and AIDS. I propose molecular and biological analyses of FeLV A, B and C and HTLV-I prototype viruses to define crucial aspects of their biological activity and the genetic features which determine these properties. Molecular studies will include transcription analysis, molecular cloning and DNA sequencing of natural virus isolates and generation of recombinent FeLV and FeLV/HTLV following in-vitro manipulation of cloned DNAs. Biological studies will include transfection and tests for transcriptional activity, virus production and ability to complement oncogenes in transformation of naive rat embryo fibroblasts. Certain viruses derived by transfection will also be inoculated into domestic cats to monitor pathogenic activity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Modified Research Career Development Award (K04)
Project #
5K04CA001058-03
Application #
3071618
Study Section
Experimental Virology Study Section (EVR)
Project Start
1985-07-01
Project End
1990-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
Schools of Public Health
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Tirotta, Emanuele; Kirby, Leslie A; Hatch, Maya N et al. (2012) IFN-?-induced apoptosis of human embryonic stem cell derived oligodendrocyte progenitor cells is restricted by CXCR2 signaling. Stem Cell Res 9:208-17
Weinger, Jason G; Weist, Brian M; Plaisted, Warren C et al. (2012) MHC mismatch results in neural progenitor cell rejection following spinal cord transplantation in a model of viral-induced demyelination. Stem Cells 30:2584-95
Newbound, G C; O'Rourke, J P; Collins, N D et al. (2000) Repression of tax-mediated human t-lymphotropic virus type 1 transcription by inducible cAMP early repressor (ICER) protein in peripheral blood mononuclear cells. J Med Virol 62:286-92
Mullins, J I; Hoover, E A; Quackenbush, S L et al. (1991) Disease progression and viral genome variants in experimental feline leukemia virus-induced immunodeficiency syndrome. J Acquir Immune Defic Syndr 4:547-57
Donahue, P R; Quackenbush, S L; Gallo, M V et al. (1991) Viral genetic determinants of T-cell killing and immunodeficiency disease induction by the feline leukemia virus FeLV-FAIDS. J Virol 65:4461-9
Shpaer, E G; Mullins, J I (1990) Selection against CpG dinucleotides in lentiviral genes: a possible role of methylation in regulation of viral expression. Nucleic Acids Res 18:5793-7
Hoover, E A; Quackenbush, S L; Poss, M L et al. (1990) Pathogenic mechanisms of immunodeficiency syndrome and aplastic anemia induced by feline leukemia viruses. Dev Biol Stand 72:163-6
Fultz, P N; Anderson, D C; McClure, H M et al. (1990) SIVsmm infection of macaque and mangabey monkeys: correlation between in vivo and in vitro properties of different isolates. Dev Biol Stand 72:253-8
Quackenbush, S L; Mullins, J I; Hoover, E A (1989) Colony forming T lymphocyte deficit in the development of feline retrovirus induced immunodeficiency syndrome. Blood 73:509-16
Mullins, J I; Hoover, E A; Overbaugh, J et al. (1989) FeLV-FAIDS-induced immunodeficiency syndrome in cats. Vet Immunol Immunopathol 21:25-37

Showing the most recent 10 out of 17 publications