title: Macrophage-tropic simian/human immunodeficiency virus chimeras use CXCR4, not CCR5, for infections of rhesus macaque peripheral blood mononuclear cells and alveolar macrophages.
abstract: After the nearly complete and irreversible depletion of CD4(+) T lymphocytes induced by highly pathogenic simian/human immunodeficiency virus chimeric viruses (SHIVs) during infections of rhesus monkeys, tissue macrophages are able to sustain high levels (>10(6) viral RNA copies/ml) of plasma viremia for several months. We recently reported that the virus present in the plasma during the late macrophage phase of infection had acquired changes that specifically targeted the V2 region of gp120 (H. Imamichi et al., Proc. Natl. Acad. Sci. USA 99:13813-13818, 2002); some of these SHIV variants were macrophage-tropic (M-tropic). Those findings have been extended by examining the tropic properties, coreceptor usage, and gp120 structure of five independent SHIVs recovered directly from lymph nodes of late-stage animals. All of these tissue-derived SHIV isolates were able to infect alveolar macrophages. These M-tropic SHIVs used CXCR4, not CCR5, for infections of rhesus monkey PBMC and primary alveolar macrophages. Because the starting highly pathogenic T-tropic SHIV inoculum also utilized CXCR4, these results indicate that the acquisition of M-tropism in the SHIV-macaque system is not accompanied by a change in coreceptor usage. Compared to the initial T-tropic SHIV inoculum, tissue-derived M-tropic SHIVs from individual infected animals carry gp120s containing similar changes (specific amino acid deletions, substitutions, and loss of N-linked glycosylation sites), primarily within the V1 and/or V2 regions of gp120.
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Olivia K
authors.initials: OK
authors.lastname: Donau
authors.forename: Hiromi
authors.initials: H
authors.lastname: Imamichi
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Dumaurier
authors.forename: Reza
authors.initials: R
authors.lastname: Sadjadpour
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Plishka
authors.forename: Alicia
authors.initials: A
authors.lastname: Buckler-White
authors.forename: Charles
authors.initials: C
authors.lastname: Buckler
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Suffredini
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane
authors.forename: John P
authors.initials: JP
authors.lastname: Moore
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Martin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008198:Lymph Nodes / Q000821:virology; D008253:Macaca mulatta; D008264:Macrophages / Q000821:virology*; D016676:Macrophages, Alveolar / Q000821:virology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D011995:Recombination, Genetic; D016097:Simian Acquired Immunodeficiency Syndrome; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics; D014779:Virus Replication
chemical_list: D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus