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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Long-term persistent infection of macaque monkeys with the simian immunodeficiency virus
M D Daniel1, N L Letvin, P K Sehgal
1New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772.
Abstract:
Juvenile rhesus macaques 6 to 18 months of age were experimentally infected by intravenous inoculation with the simian immunodeficiency virus (SIV), the T cell-tropic retrovirus of monkeys related to the human acquired immunodeficiency syndrome (AIDS) virus HIV. The SIV used for inoculation was grown either in normal human peripheral blood lymphocytes in the presence of interleukin 2 or in the human tumour cell line HUT-78. Eight of the macaques died 129 to 352 days post-inoculation with a variety of clinical and pathological findings paralleling those of AIDS in humans. However eight other animals became persistently infected for prolonged periods; these eight macaques remained alive at 537 and 820 days post-inoculation despite persistent lymphadenopathy and our continued ability to isolate SIV. The ability of these monkeys to survive infection correlated directly with the strength of their antibody response to SIV. Infection was also established in macaques using approximately 100 tissue culture infectious doses of HUT-78-grown SIV. There was no correlation between the dose of virus inoculum and either the strength of the antibody response or clinical outcome. These results demonstrate that SIV infection of macaques can be used not only to study acute AIDS but also to mimic the long-term persistent infection seen in carriers of HIV.
Insights
Simian immunodeficiency virus (SIV) infection in macaques can mimic human AIDS. Macaque survival depends on their antibody response to SIV, not the virus dose.
Area of Science:
- Virology
- Immunology
- Primatology
Background:
- Simian immunodeficiency virus (SIV) is a retrovirus related to HIV, the cause of AIDS.
- SIV infects T cells and can cause disease in non-human primates.
- Understanding SIV pathogenesis is crucial for developing AIDS therapies.
Purpose of the Study:
- To investigate the effects of SIV infection in juvenile rhesus macaques.
- To explore the correlation between antibody response, virus dose, and clinical outcome.
- To establish a macaque model for studying both acute and persistent HIV/AIDS.
Main Methods:
- Experimental intravenous inoculation of juvenile rhesus macaques with SIV.
- SIV cultured in human lymphocytes with interleukin 2 or the HUT-78 cell line.
- Monitoring of clinical signs, pathological findings, and antibody responses post-inoculation.
Main Results:
- Eight of ten macaques died between 129-352 days post-inoculation with AIDS-like symptoms.
- The remaining eight macaques survived long-term (537-820 days) with persistent SIV infection.
- Stronger antibody response to SIV correlated with prolonged survival.
- No correlation was found between virus inoculum dose and antibody response or clinical outcome.
Conclusions:
- SIV-infected macaques serve as a valuable model for studying AIDS.
- Macaque antibody response to SIV is a key factor in determining disease progression.
- This model can elucidate mechanisms of both acute and chronic HIV infection.
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