Related Experiment Video
Updated: Aug 9, 2026
A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
Suppression of human immunodeficiency virus replication by CD8+ cells from infected and uninfected chimpanzees
B A Castro1, C M Walker, J W Eichberg
1Cancer Research Institute, University of California, San Francisco 94143-0128.
Insights
Chimpanzee CD8+ cells suppress human immunodeficiency virus type 1 (HIV-1) replication, explaining their natural resistance to HIV-induced disease. This finding contrasts with previous observations in humans.
Area of Science:
- Immunology
- Virology
- Primatology
Background:
- Human immunodeficiency virus type 1 (HIV-1) infection in animals typically shows intermittent virus recovery at low titers.
- The mechanism behind this limited viral replication in certain animal models remains unclear.
Purpose of the Study:
- To investigate the role of specific immune cells in controlling HIV-1 replication in animals.
- To understand the potential mechanisms contributing to natural resistance against HIV-1 infection.
Main Methods:
- Peripheral blood mononuclear cells (PBMC) from infected animals were cultured after depletion or enrichment of CD4+ and CD8+ cells.
- Purified CD8+ effector cells were added to HIV-1-infected CD4+ target cells to assess viral suppression.
- Viral replication levels were quantified to evaluate the impact of cell manipulation.
Main Results:
- Depleting CD8+ cells or enriching CD4+ cells significantly increased HIV-1 recovery and replication frequency.
- Addition of CD8+ cells from both infected and uninfected animals markedly suppressed HIV-1 production in CD4+ cells.
- CD8+ cells from chimpanzees demonstrated potent HIV-1-suppressing activity, unlike those from seronegative humans.
Conclusions:
- CD8+ cell-mediated suppression of viral replication is a key factor in the natural resistance of chimpanzees to HIV-1.
- These findings offer insights into host-pathogen interactions and potential therapeutic strategies for HIV-1.
Abstract:
Over a 4-year period, infectious human immunodeficiency virus type 1 (HIV-1) has been recovered from cultured peripheral blood mononuclear cells (PBMC) of virus-infected animals only intermittently and at relatively low titers. In examining the possible mechanism for this observation, CD4+ cells or CD8+ cells were removed by panning from the PMBC before culture. A dramatic increase in frequency of HIV-1 recovery as well as in the level of virus replication was observed in the CD4+ cell-enriched or CD8+ cell-depleted cultures of PBMC from 3/3 infected animals. Moreover, addition of purified CD8+ effector cells from all 6 HIV-infected and 5/10 uninfected animals to an equal number of HIV-1 acutely infected purified CD4+ target cells resulted in 75-100% suppression of virus production. CD8+ cells from 3 additional uninfected animals caused delayed replication kinetics and moderate to low suppression of peak virus production. These findings contrast with the previously recognized absence of this HIV-1-suppressing activity of CD8+ cells from seronegative humans. This CD8+ cell-mediated suppression of viral replication could help explain the natural resistance of chimpanzees to HIV-induced disease.
