Based on the concept of anti-sense RNA expression, we plan to establish and characterize systems which exhibit resistance to animal virus infection. 1.) Using bovine papilloma virus vectors, we will further develop permanent cell lines (C127) which express high levels of influenza virus genes in the anti-sense. These cells will be examined for their ability prevent replication of influenza viruses. In addition, we will establish cell lines which express anti-sense RNAs from tandem copies of full length and/or of domains of influenza virus genes. Such cell lines may show an enhanced resistance to influenza virus infection because of gene dosage effect of the anti-sense RNAs. Cell lines permanently expressing RNAs analogous to defective interfering (DI) RNAs of influenza virus will also be examined for their ability to interfere with viral replication. 2.) We will test alternative cell, vector and promoter systems such as 293 cells and EBV-based vectors containing CMV promoters to express virus-specific anti-sense RNAs in order to establish optimal resistance conditions and to allow infection with different influenza viruses. 3.) We will study the mechanism of action by which anti-sense RNA expression inhibits influenza virus replication. 4.) We will attempt to generate transgenic mice made resistant to influenza virus infection via anti-sense RNA expression. 5.) To determine the usefulness of anti-sense RNA expression as a general antiviral approach, we will try to establish a second viral anti-sense RNA expression system by introducing a vesicular stomatitis virus (VSV) gene into tissue culture cells. 6.) We will attempt to develop ribo- and/or deoxyribo- oligonucleotides which are complementary to influenza virus- specific sequences, for use as antiviral agents.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mount Sinai School of Medicine
New York
United States
Zip Code
Isobe, H; Moran, T; Li, S et al. (1995) Presentation by a major histocompatibility complex class I molecule of nucleoprotein peptide expressed in two different genes of an influenza virus transfectant. J Exp Med 181:203-13
Zaghouani, H; Anderson, S A; Sperber, K E et al. (1995) Induction of antibodies to the human immunodeficiency virus type 1 by immunization of baboons with immunoglobulin molecules carrying the principal neutralizing determinant of the envelope protein. Proc Natl Acad Sci U S A 92:631-5
Rodrigues, M; Li, S; Murata, K et al. (1994) Influenza and vaccinia viruses expressing malaria CD8+ T and B cell epitopes. Comparison of their immunogenicity and capacity to induce protective immunity. J Immunol 153:4636-48
Zaghouani, H; Steinman, R; Nonacs, R et al. (1993) Presentation of a viral T cell epitope expressed in the CDR3 region of a self immunoglobulin molecule. Science 259:224-7
Macri, P; Gordon, J W (1993) Transgenic animals as tools for investigating hepatocyte gene regulation and liver disease. Prog Liver Dis 11:1-25
Kuzu, H; Kuzu, Y; Zaghouani, H et al. (1993) In vivo priming effect during various stages of ontogeny of an influenza A virus nucleoprotein peptide. Eur J Immunol 23:1397-400
Kuzu, Y; Kuzu, H; Zaghouani, H et al. (1993) Priming of cytotoxic T lymphocytes at various stages of ontogeny with transfectoma cells expressing a chimeric Ig heavy chain gene bearing an influenza virus nucleoprotein peptide. Int Immunol 5:1301-7
Brumeanu, T D; Kohanski, R; Bona, C A et al. (1993) A sensitive method to detect defined peptide among those eluted from murine MHC class II molecules. J Immunol Methods 160:65-71
Li, S; Polonis, V; Isobe, H et al. (1993) Chimeric influenza virus induces neutralizing antibodies and cytotoxic T cells against human immunodeficiency virus type 1. J Virol 67:6659-66
Li, S; Rodrigues, M; Rodriguez, D et al. (1993) Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria. Proc Natl Acad Sci U S A 90:5214-8

Showing the most recent 10 out of 22 publications