Dose-Response Resistance to HIV-1/MuLV Pseudotype Virus ex vivo in a Hairpin Ribozyme Transgenic Mouse Model

We have investigated the efficacy of a hairpin ribozyme targeting the 5′ leader sequence of HIV-1 RNA in a transgenic model system. Primary spleen cells derived from transgenic or control mice were infected with HIV-1/MuLV pseudotype virus. A significantly reduced susceptibility to infection in ribo...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1999-10, Vol.96 (22), p.12749-12753
Main Authors: Andäng, Michael, Hinkula, Jorma, Hotchkiss, Graham, Larsson, Sten, Britton, Sven, Wong-Staal, Flossie, Wahren, Britta, Ahrlund-Richter, Lars
Format: Article
Language:English
Subjects:
AIDS/HIV
Animals
Antigens
Base Sequence
Biological Sciences
Cell lines
Cytomegalovirus - genetics
Disease Models, Animal
DNA Primers
Dose-Response Relationship, Drug
Drug Resistance, Microbial
Gene therapy
HIV
HIV 1
HIV-1 - drug effects
Human immunodeficiency virus
Human immunodeficiency virus 1
Infections
Leukemia Virus, Murine - drug effects
Medicin och hälsovetenskap
Mice
Mice, Transgenic
Oligonucleotides, Antisense - pharmacology
Ribonucleic acid
ribozymes
RNA
RNA, Catalytic - genetics
Rodents
Spleen
Spleen cells
T lymphocytes
Transgenic animals
Viruses
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Summary:We have investigated the efficacy of a hairpin ribozyme targeting the 5′ leader sequence of HIV-1 RNA in a transgenic model system. Primary spleen cells derived from transgenic or control mice were infected with HIV-1/MuLV pseudotype virus. A significantly reduced susceptibility to infection in ribozyme-expressing transgenic spleen cells (P = 0.01) was shown. Variation of transgene-expression levels between littermates revealed a dose response between ribozyme expression and viral resistance, with an estimated cut off value below 0.2 copies of hairpin ribozyme per cell. These findings open up possibilities for studies on ribozyme efficacy and anti-HIV-1 gene therapy.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.96.22.12749