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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 22; pp. 12749 - 12753
• Main Authors: Andäng, Michael, Hinkula, Jorma, Hotchkiss, Graham, Larsson, Sten, Britton, Sven, Wong-Staal, Flossie, Wahren, Britta, Ahrlund-Richter, Lars
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 26.10.1999; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• 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
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.22.12749

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.