Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue
<p>Abstract</p> <p>Background</p> <p>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...
| Հիմնական հեղինակներ: | , , , , , , |
|---|---|
| Ձևաչափ: | Հոդված |
| Լեզու: | English |
| Հրապարակվել է: |
BMC
2012-03-01
|
| Շարք: | Retrovirology |
| Խորագրեր: | |
| Առցանց հասանելիություն: | http://www.retrovirology.com/content/9/1/20 |
| _version_ | 1831597217206501376 |
|---|---|
| author | Gonzalez-Perez Maria O'Connell Olivia Lin Rongheng Sullivan W Matthew Bell Jeanne Simmonds Peter Clapham Paul R |
| author_facet | Gonzalez-Perez Maria O'Connell Olivia Lin Rongheng Sullivan W Matthew Bell Jeanne Simmonds Peter Clapham Paul R |
| author_sort | Gonzalez-Perez Maria |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-18T13:41:13Z |
| format | Article |
| id | doaj.art-c8f8506985ca4fb890b28e31a47e23d0 |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-12-18T13:41:13Z |
| publishDate | 2012-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-c8f8506985ca4fb890b28e31a47e23d02022-12-21T21:05:50ZengBMCRetrovirology1742-46902012-03-01912010.1186/1742-4690-9-20Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissueGonzalez-Perez MariaO'Connell OliviaLin RonghengSullivan W MatthewBell JeanneSimmonds PeterClapham Paul R<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>http://www.retrovirology.com/content/9/1/20HIVEnvelopeMacrophage-tropismCD4CCR5NeurotropismImmune tissueBrainEntry |
| spellingShingle | Gonzalez-Perez Maria O'Connell Olivia Lin Rongheng Sullivan W Matthew Bell Jeanne Simmonds Peter Clapham Paul R Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue Retrovirology HIV Envelope Macrophage-tropism CD4 CCR5 Neurotropism Immune tissue Brain Entry |
| title | Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue |
| title_full | Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue |
| title_fullStr | Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue |
| title_full_unstemmed | Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue |
| title_short | Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue |
| title_sort | independent evolution of macrophage tropism and increased charge between hiv 1 r5 envelopes present in brain and immune tissue |
| topic | HIV Envelope Macrophage-tropism CD4 CCR5 Neurotropism Immune tissue Brain Entry |
| url | http://www.retrovirology.com/content/9/1/20 |
| work_keys_str_mv | AT gonzalezperezmaria independentevolutionofmacrophagetropismandincreasedchargebetweenhiv1r5envelopespresentinbrainandimmunetissue AT oconnellolivia independentevolutionofmacrophagetropismandincreasedchargebetweenhiv1r5envelopespresentinbrainandimmunetissue AT linrongheng independentevolutionofmacrophagetropismandincreasedchargebetweenhiv1r5envelopespresentinbrainandimmunetissue AT sullivanwmatthew independentevolutionofmacrophagetropismandincreasedchargebetweenhiv1r5envelopespresentinbrainandimmunetissue AT belljeanne independentevolutionofmacrophagetropismandincreasedchargebetweenhiv1r5envelopespresentinbrainandimmunetissue AT simmondspeter independentevolutionofmacrophagetropismandincreasedchargebetweenhiv1r5envelopespresentinbrainandimmunetissue AT claphampaulr independentevolutionofmacrophagetropismandincreasedchargebetweenhiv1r5envelopespresentinbrainandimmunetissue |