title: Modulation of HIV-1 macrophage-tropism among R5 envelopes occurs before detection of neutralizing antibodies.
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.
authors.affiliation: Program in Molecular Medicine and Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Biotech 2, 373 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Kathryn H
authors.initials: KH
authors.lastname: Richards
authors.forename: Marlén Mi
authors.initials: MM
authors.lastname: Aasa-Chapman
authors.forename: Aine
authors.initials: A
authors.lastname: McKnight
authors.forename: Paul R
authors.initials: PR
authors.lastname: Clapham
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D002478:Cells, Cultured; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008131:London; D008264:Macrophages / Q000821:virology*; D056189:Viral Tropism; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus