Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue

التفاصيل البيبلوغرافية
العنوان: Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue
المؤلفون: Gonzalez-Perez, Maria, O'Connell, Olivia, Lin, Rongheng, Sullivan, W Matthew, Bell, Jeanne, Simmonds, Peter, Clapham, Paul R
بيانات النشر: BioMed Central Ltd.
سنة النشر: 2012
المجموعة: BioMed Central
مصطلحات موضوعية: HIV, Envelope, Macrophage-tropism, CD4, CCR5, Neurotropism, Immune tissue, Brain, Entry
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: report
اللغة: English
العلاقة: http://www.retrovirology.com/content/9/1/20Test
الإتاحة: http://www.retrovirology.com/content/9/1/20Test
حقوق: Copyright 2012 Gonzalez-Perez et al; licensee BioMed Central Ltd.
رقم الانضمام: edsbas.4698046B
قاعدة البيانات: BASE