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.
Igarashi
Tatsuhiko
T
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Imamichi
Hiromi
H
Brown
Charles R
CR
Hirsch
Vanessa M
VM
Martin
Malcolm A
MA
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