The emergence and characterization of macrophage-tropic SIV/HIV chimeric viruses (SHIVs) present in CD4+ T cell-depleted rhesus monkeys.
Highly pathogenic simian immunodeficiency virus/human immunodeficiency virus type 1 chimeric viruses (SHIVs) induce an extremely rapid, systemic, and irreversible depletion of CD4+ T lymphocytes following their inoculation into rhesus macaques. Confocal fluorescence microscopy was used to demonstrate that high levels of viremia in infected animals were sustained by virus-producing tissue macrophage (mphi) following the irreversible elimination of CD4+ T lymphocytes by highly pathogenic SHIVDH12R. The envelope glycoproteins carried by plasma virus in CD4-depleted animals were found to contain specific alterations affecting the V2 region of gp120; similar V2 changes were observed during independent monkey infections. The altered V2 loops contained double amino acid deletions and the loss of a highly conserved N-linked glycosylation site. In contrast to the starting highly pathogenic SHIV, which is exclusively T cell-tropic, some mphi-phase SHIVs, bearing altered V2 regions, were able to establish spreading infections of cultured alveolar mphi.
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Tatsuhiko
T
Igarashi
Hiromi
H
Imamichi
Charles R
CR
Brown
Vanessa M
VM
Hirsch
Malcolm A
MA
Martin
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016827:CD8 Antigens / Q000276:immunology; D002678:Chimera; D016679:Genome, Viral; D006678:HIV / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D019562:Viral Load; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics; D014779:Virus Replication / Q000502:physiology*
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D014764:Viral Proteins