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Serial in vivo passage of HIV-1 infection in Macaca nemestrina
M B Agy1, A Schmidt, M J Florey
1Regional Primate Research Center, University of Washington, Seattle 98195, USA. magy@u.washington.edu
Abstract:
In an earlier study we found that pigtailed macaques (Macaca nemestrina) that were experimentally infected with human immunodeficiency virus type 1 (HIV-1) initially became viremic and seroconverted, but HIV-1 replication diminished markedly over time. In an attempt to develop a longer term pathogenic model, blood from HIV-1-infected macaques was serially transfused into three groups of naive macaques. Transfer was successful through two transfusions as shown by repeated virus isolations and confirmed by the development of cell-free plasma viremia and by seroconversion. Three to five weeks after transfusion, plasma levels of HIV-1 RNA from several macaques in the first two groups exceeded those of the initially inoculated macaques. However, animals in the third group had diminished RNA levels, were virus culture negative, and did not seroconvert. Sequence analyses of env-region clones from infected animals revealed only minimal changes over the course of the passages. These results confirm HIV-1 replication in M. nemestrina during the acute phase of infection. However, adaptation of HIV-1 to a macaque-pathogenic variant did not occur during serial passage, possibly because the animals were able to restrict HIV-1 replication below a level required for a pathogenic variant to emerge. Whether such containment is a function of the host's immune response or a virus cell incompatibility remains to be determined.
Insights
Serial passage of human immunodeficiency virus type 1 (HIV-1) in macaques did not create a pathogenic model. Macaques controlled HIV-1 replication, preventing the emergence of a more virulent virus strain.
Area of Science:
- Virology
- Immunology
- Primate Models
Background:
- Previous studies showed pigtailed macaques (Macaca nemestrina) infected with human immunodeficiency virus type 1 (HIV-1) experienced initial viremia and seroconversion, followed by diminished viral replication.
- Developing a longer-term pathogenic model for HIV-1 in macaques is crucial for understanding disease progression and testing interventions.
Purpose of the Study:
- To investigate the potential for serial passage of HIV-1 in naive macaques to establish a persistent, pathogenic infection model.
- To determine if HIV-1 can adapt and evolve into a more pathogenic variant within the macaque host through serial blood transfusions.
Main Methods:
- Experimentally infected macaques' blood was serially transfused into groups of naive macaques.
- Viral isolation, plasma HIV-1 RNA quantification, and serological assays were used to confirm successful virus transfer and infection.
- Sequence analysis of the HIV-1 env-region was performed to detect viral evolution across passages.
Main Results:
- Successful HIV-1 transfer and viremia were confirmed through two serial passages.
- Plasma HIV-1 RNA levels increased in some macaques after transfusion, exceeding initial levels.
- The third group of macaques showed diminished RNA levels, negative virus cultures, and no seroconversion, indicating viral containment.
- Sequence analysis revealed minimal changes in the env-region, suggesting a lack of significant viral adaptation.
Conclusions:
- HIV-1 replicates in Macaca nemestrina during the acute phase of infection.
- Serial passage did not lead to the adaptation of HIV-1 into a pathogenic macaque-pathogenic variant.
- Macaques appear to restrict HIV-1 replication, potentially hindering the emergence of a more virulent strain, possibly due to immune responses or viral-host incompatibility.