دورية أكاديمية
Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue
| العنوان: | Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue |
|---|---|
| المؤلفون: | Gonzalez-Perez, Maria Paz, O’Connell, Olivia, Lin, Rongheng, Sullivan, W Matthew, Bell, Jeanne, Simmonds, Peter, Clapham, Paul R |
| المصدر: | Rongheng Lin |
| بيانات النشر: | SelectedWorks |
| سنة النشر: | 2012 |
| المجموعة: | University of Massachusetts: ScholarWorks@UMass Amherst |
| مصطلحات موضوعية: | HIV, Envelope, Macrophage-tropism, CD4, CCR5, Neurotropism, Immune tissue, Brain, Entry, HIV-1, Public Health |
| الوصف: | 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 ... |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://works.bepress.com/rongheng_lin/5Test; https://works.bepress.com/context/rongheng_lin/article/1006/viewcontent/Independent_evolution_of_macrophage_tropism_and_increased_charge_between_HIV_1_R5_enveloopes_present_in_brain_and_immune_tissue.pdfTest |
| الإتاحة: | https://works.bepress.com/rongheng_lin/5Test https://works.bepress.com/context/rongheng_lin/article/1006/viewcontent/Independent_evolution_of_macrophage_tropism_and_increased_charge_between_HIV_1_R5_enveloopes_present_in_brain_and_immune_tissue.pdfTest |
| رقم الانضمام: | edsbas.B71FD336 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |