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dc.contributor.authorGonzalez-Perez, Maria Paz
dc.contributor.authorO'Connell, Olivia
dc.contributor.authorLin, Rongheng
dc.contributor.authorSullivan, W. Matthew
dc.contributor.authorBell, Jeanne E.
dc.contributor.authorSimmonds, Peter
dc.contributor.authorClapham, Paul R.
dc.date2022-08-11T08:09:40.000
dc.date.accessioned2022-08-23T16:39:42Z
dc.date.available2022-08-23T16:39:42Z
dc.date.issued2012-03-15
dc.date.submitted2012-08-27
dc.identifier.citationRetrovirology. 2012 Mar 15;9:20. <a href="http://dx.doi.org/10.1186/1742-4690-9-20" target="_blank">Link to article on publisher's site</a>
dc.identifier.issn1742-4690 (Linking)
dc.identifier.doi10.1186/1742-4690-9-20
dc.identifier.pmid22420378
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39530
dc.description.abstractBACKGROUND: 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=22420378&dopt=Abstract">Link to Article in PubMed</a>
dc.rights© 2012 Gonzalez-Perez et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.subjectAcquired Immunodeficiency Syndrome
dc.subjectBrain
dc.subjectHIV Envelope Protein gp120
dc.subjectHIV-1
dc.subjectMacrophages
dc.subjectViral Tropism
dc.subjectImmunology and Infectious Disease
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.subjectVirology
dc.subjectVirus Diseases
dc.titleIndependent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue
dc.typeJournal Article
dc.source.journaltitleRetrovirology
dc.source.volume9
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3324&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2324
dc.identifier.contextkey3266172
refterms.dateFOA2022-08-23T16:39:42Z
html.description.abstract<p>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.</p> <p>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.</p> <p>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.</p>
dc.identifier.submissionpathoapubs/2324
dc.contributor.departmentDepartment of Microbiology and Physiological Systems
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages20


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