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Viremia and AIDS in rhesus macaques after intramuscular inoculation of plasmid DNA encoding full-length SIVmac239
V Liska1, A H Khimani, R Hofmann-Lehmann
1Laboratory of Viral Pathogenesis, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Abstract:
We have succeeded in stably maintaining the entire genome of SIVmac239 as a plasmid clone. Supercoiled proviral plasmid DNA was inoculated intramuscularly into two adult rhesus macaques and into a neonate. All three animals became viremic and seroconverted. Viral kinetics were followed prospectively by quantitative competitive reverse transcriptase polymerase chain reaction (QC-RT-PCR), measurement of proviral DNA load in peripheral blood mononuclear cells (PBMCs) by PCR, and virus isolation by cocultivation. The infant developed high virus loads and succumbed to AIDS and SIV-associated nephropathy at 10 weeks postinoculation. Both adults are still living but have progressed to AIDS; one adult has also developed severe thrombocytopenia. We conclude that infection through intramuscular inoculation of cloned plasmid DNA encoding the entire proviral genome is reproducible and will provide a useful tool for studying viral pathogenesis.
Insights
Researchers created a stable SIVmac239 plasmid clone. Intramuscular inoculation in macaques caused viremia, AIDS, and disease, demonstrating a reproducible model for studying simian immunodeficiency virus (SIV) pathogenesis.
Area of Science:
- Virology
- Immunology
- Primate Models
Background:
- Simian immunodeficiency virus (SIV) infection in macaques serves as a critical model for understanding human immunodeficiency virus (HIV) pathogenesis.
- Developing reproducible methods for SIV infection is essential for advancing research into viral diseases.
Purpose of the Study:
- To establish a stable plasmid clone of the SIVmac239 genome.
- To assess the infectivity and pathogenicity of intramuscular inoculation of cloned SIVmac239 proviral DNA in rhesus macaques.
Main Methods:
- Generation of a stable plasmid clone containing the full SIVmac239 genome.
- Intramuscular inoculation of cloned proviral DNA into adult and neonatal rhesus macaques.
- Longitudinal monitoring of viral kinetics using quantitative competitive reverse transcriptase polymerase chain reaction (QC-RT-PCR), proviral DNA load in peripheral blood mononuclear cells (PBMCs), and virus isolation.
Main Results:
- All inoculated macaques (two adults, one neonate) developed viremia and seroconverted.
- The infant macaque succumbed to acquired immunodeficiency syndrome (AIDS) and SIV-associated nephropathy within 10 weeks.
- Adult macaques progressed to AIDS, with one developing severe thrombocytopenia, indicating significant disease progression.
Conclusions:
- Intramuscular inoculation of cloned SIVmac239 DNA is a reproducible method for establishing SIV infection in macaques.
- This approach provides a valuable and reproducible tool for studying SIV pathogenesis and developing therapeutic strategies.