Macrophage-tropic simian/human immunodeficiency virus chimeras use CXCR4, not CCR5, for infections of rhesus macaque peripheral blood mononuclear cells and alveolar macrophages.
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.
Igarashi
Tatsuhiko
T
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Donau
Olivia K
OK
Imamichi
Hiromi
H
Dumaurier
Marie-Jeanne
MJ
Sadjadpour
Reza
R
Plishka
Ronald J
RJ
Buckler-White
Alicia
A
Buckler
Charles
C
Suffredini
Anthony F
AF
Lane
H Clifford
HC
Moore
John P
JP
Martin
Malcolm A
MA
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
D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus