Dropulic B, Dickie P, Jeang KT; National Conference on Human Retroviruses and Related Infections.
Program Abstr First Natl Conf Hum Retrovir Relat Infect Natl Conf Hum Retrovir Relat Infect 1st 1993 Wash DC. 1993 Dec 12-16; 148.
National Institute of Allergy and Infectious Diseases, Bethesda, MD.
Ribozymes are catalytic RNAs that specifically cleave complementary target RNAs. We have shown previously that when a U5 ribozyme is placed in the Nef gene of the HIV-1 genome, virus replication could be initially inhibited in tissue culture. The HIV genomic model is useful since it allows for in vivo mapping of HIV ribozyme sensitive sites. We have now mapped several other potential target sites in the HIV-RNA and characterized their sensitivity to ribozymes. We found that HIV ribozyme site sensitivity correlated with whether the sequences were found on spliced or unspliced HIV-RNAs. In addition, we have examined the ability of ribozyme containing HIV genomes to dominantly interfere with the wild-type virus. We found that ribozyme containing HIV genomes can dominantly interfere with wild- type HIV replication in vivo. Finally, we have created a transgenic mouse line which expresses the U5 ribozyme. These mice have been mated with a transgenic line which expresses HIV-RNA. Preliminary data suggest that the progeny resulting from the HIV/U5 ribozyme transgenic crosses show a delay in the onset of a nephritic pathology that normally develops in the parental HIV transgenic line.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Animals
- Antiviral Agents
- Base Sequence
- Genes, nef
- HIV
- HIV Infections
- HIV Seropositivity
- HIV-1
- Mice
- RNA, Catalytic
- Virus Replication
- genetics
- virology
Other ID:
UI: 102214478
From Meeting Abstracts