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Modulation of HIV-1 macrophage-tropism among R5 envelopes occurs before detection of neutralizing antibodies

Richards, KH; Aasa-Chapman, MMI; McKnight, A; Clapham, PR; (2010) Modulation of HIV-1 macrophage-tropism among R5 envelopes occurs before detection of neutralizing antibodies. Retrovirology , 7 , Article 48. 10.1186/1742-4690-7-48. Green open access

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Abstract

HIV-1 R5 viruses vary widely in their capacity to infect primary macrophages. R5 macrophage-tropism is associated with an increased envelope:CD4 affinity that partly results from an increased exposure of CD4 contact residues on gp120 and allows the use of low levels of CD4 for infection. The selective pressures in vivo that modulate R5 macrophage-tropism are not understood. It is possible that different R5 variants adapt for replication in either T-cells (high CD4) or in macrophages (low CD4). However, other selective pressures in vivo (e.g. neutralizing antibodies) may also impact R5 tropism. Here, we measured macrophage infectivity conferred by gp120 sequences amplified sequentially from subjects in London followed from the acute stage of infection. We report wide variation in the capacity of these envelopes to confer macrophage infection in the complete absence of both autologous and heterologous neutralizing antibodies. Our data show that the variation in macrophage tropism observed at early times cannot have been influenced by neutralizing antibodies.

Type: Article
Title: Modulation of HIV-1 macrophage-tropism among R5 envelopes occurs before detection of neutralizing antibodies
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1742-4690-7-48
Publisher version: http://dx.doi.org/10.1186/1742-4690-7-48
Language: English
Additional information: © 2010 Richards 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.
Keywords: Immunodeficiency-virus Type-1, Monocyte-derived macrophages, Central-nervous-system, CD4 binding loop, Lymphoid-tissues, Brain, Infection, CCR5, Sensitivity, Blood
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/123210
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