Program in Molecular Medicine; Department of Molecular Genetics and Microbiology
Antibodies, Neutralizing; Cells, Cultured; HIV Antibodies; HIV Infections; HIV-1; Humans; London; Macrophages; *Viral Tropism; env Gene Products, Human Immunodeficiency Virus
Life Sciences | Medicine and Health Sciences | Virology
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.
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Citation: Retrovirology. 2010 May 27;7:48. Link to article on publisher's site
Richards, Kathryn H.; Aasa-Chapman, Marlen M.I.; McKnight, Aine; and Clapham, Paul R., "Modulation of HIV-1 macrophage-tropism among R5 envelopes occurs before detection of neutralizing antibodies" (2010). Open Access Articles. Paper 2226.