Abstract

Malignant rabbit fibroma virus (MV) infects and relicates in lymphocytes, is profoundly immunosuppressive, and causes disseminated tumors. Shope fibroma virus (SFV) is related to MV, but causes only local tumors and does not replicate in lymphocytes. We propose here to study the nature of the gene(s) in MV that determine its ability to infect and replicate in lymphocytes. Inserting into SFV the DNA from the """"""""C"""""""" restriction fragment that results from BAM HI digestion of MV transfers to SFV the ability to replicate in lymphocytes and to suppress the immunologic function of these target lymphocytes. We propose to determine which gene(s) on this fragment is responsible for this function, the nature of the product of this gene, and the mechanism of action of the encoded protein. Host factors that may play a role in MV infection of lymphocytes will also be examined. The accomplishment of these goals will permit us to understand the genetic and molecular basis for the ability of lymphocytotrophic virus to ineect and replicate in lymphocytes, and perhaps provide us with greater understanding for the role of immunosuppression in the dissemination of tumors of viral origin.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA044800-02
Application #
3187604
Study Section
Experimental Virology Study Section (EVR)
Project Start
1988-03-01
Project End
1991-02-28
Budget Start
1989-03-01
Budget End
1990-02-28
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225

  Publications

Duan, Yu-You; Wu, Jian; Zhu, Jian-Liang et al. (2004) Gene therapy for human alpha1-antitrypsin deficiency in an animal model using SV40-derived vectors. Gastroenterology 127:1222-32
Strayer, D S; Lamothe, M; Wei, D et al. (2001) Generation of recombinant SV40 vectors for gene transfer. Methods Mol Biol 165:103-17
Strayer, D S (2000) Effective gene transfer using viral vectors based on SV40. Methods Mol Biol 133:61-74
Wali, A; Strayer, D S (1999) Comparative effects of virulent and avirulent poxviruses on cell cycle progression. Exp Mol Pathol 66:31-8
Zern, M A; Ozaki, I; Duan, L et al. (1999) A novel SV40-based vector successfully transduces and expresses an alpha 1-antitrypsin ribozyme in a human hepatoma-derived cell line. Gene Ther 6:114-20
Wali, A; Strayer, D S (1999) Infection with vaccinia virus alters regulation of cell cycle progression. DNA Cell Biol 18:837-43
Kondo, R; Feitelson, M A; Strayer, D S (1998) Use of SV40 to immunize against hepatitis B surface antigen: implications for the use of SV40 for gene transduction and its use as an immunizing agent. Gene Ther 5:575-82
Milano Jr, J; Strayer, D S (1998) Effects of overexpression of Ran/TC4 mammalian cells in vitro. Exp Cell Res 239:31-9
Strayer, D S; Kondo, R; Milano, J et al. (1997) Use of SV40-based vectors to transduce foreign genes to normal human peripheral blood mononuclear cells. Gene Ther 4:219-25
Strayer, D S; Duan, L X; Ozaki, I et al. (1997) Titering replication-defective virus for use in gene transfer. Biotechniques 22:447-50

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