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Updated: May 24, 2026
Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1
Published on: September 5, 2016
Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and
Maria Paz Gonzalez-Perez1, Olivia O'Connell, Rongheng Lin
1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01605-2377, USA.
Background:
Transmitted HIV-1 clade B or C R5 viruses have been reported to infect macrophages inefficiently, while other studies have described R5 viruses in late disease with either an enhanced macrophage-tropism or carrying envelopes with an increased positive charge and fitness. In contrast, our previous data suggested that viruses carrying non-macrophage-tropic R5 envelopes were still predominant in immune tissue of AIDS patients. To further investigate the tropism and charge of HIV-1 viruses in late disease, we evaluated the properties of HIV-1 envelopes amplified from immune and brain tissues of AIDS patients with neurological complications.
Results:
Almost all envelopes amplified were R5. There was clear compartmentalization of envelope sequences for four of the five subjects. However, strong compartmentalization of macrophage-tropism in brain was observed even when brain and immune tissue envelope sequences were not segregated. R5 envelopes from immune tissue of four subjects carried a higher positive charge compared to brain envelopes. We also confirm a significant correlation between macrophage tropism and sensitivity to soluble CD4, a weak association with sensitivity to the CD4 binding site antibody, b12, but no clear relationship with maraviroc sensitivity.
Conclusions:
Our study shows that non-macrophage-tropic R5 envelopes carrying gp120s with an increased positive charge were predominant in immune tissue in late disease. However, highly macrophage-tropic variants with lower charged gp120s were nearly universal in the brain. These results are consistent with HIV-1 R5 envelopes evolving gp120s with an increased positive charge in immune tissue or sites outside the brain that likely reflect an adaptation for increased replication or fitness for CD4+ T-cells. Our data are consistent with the presence of powerful pressures in brain and in immune tissues selecting for R5 envelopes with very different properties; high macrophage-tropism, sCD4 sensitivity and low positive charge in brain and non-macrophage-tropism, sCD4 resistance and high positive charge in immune tissue.
Insights
In late-stage AIDS, HIV-1 R5 envelopes in immune tissues show higher positive charge and non-macrophage tropism, while brain tissues harbor highly macrophage-tropic variants with lower positive charge.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- HIV-1 R5 viruses exhibit variable macrophage tropism in late-stage disease.
- Previous studies show conflicting data on R5 virus tropism and envelope properties in AIDS patients.
- Our prior work indicated non-macrophage-tropic R5 envelopes predominate in immune tissues of AIDS patients.
Purpose of the Study:
- To investigate the tropism and charge of HIV-1 envelopes in immune and brain tissues of AIDS patients with neurological complications.
- To understand the evolution of HIV-1 envelope properties in different tissue compartments during late-stage disease.
Main Methods:
- Amplification of HIV-1 envelopes from immune and brain tissues of AIDS patients.
- Analysis of envelope sequences for R5 tropism and compartmentalization.
- Assessment of envelope positive charge and sensitivity to soluble CD4 (sCD4) and b12 antibody.
Main Results:
- Nearly all amplified envelopes were R5, with significant compartmentalization observed in four of five subjects.
- Immune tissue R5 envelopes had a higher positive charge than brain envelopes.
- Macrophage tropism correlated with sCD4 sensitivity but not with b12 or maraviroc sensitivity.
Conclusions:
- Non-macrophage-tropic R5 envelopes with increased positive charge dominate immune tissues in late-stage AIDS.
- Highly macrophage-tropic variants with lower positive charge are prevalent in the brain.
- Distinct tissue-specific pressures select for divergent HIV-1 R5 envelope properties in the brain and immune tissues.
