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(Journal of Leukocyte Biology. 2003;74:772-780.)
© 2003 by Society for Leukocyte Biology

The emergence and characterization of macrophage-tropic SIV/HIV chimeric viruses (SHIVs) present in CD4⁺ T cell-depleted rhesus monkeys

Tatsuhiko Igarashi^*, Hiromi Imamichi, Charles R. Brown^*, Vanessa M. Hirsch^* and Malcolm A. Martin^*,1

^* Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; and
Science Applications International Corporation-Frederick, Inc., Frederick, Maryland

¹Correspondence: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. E-mail: malm{at}nih.gov

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 (m) following the irreversible elimination of CD4⁺ T lymphocytes by highly pathogenic SHIV_DH12R. 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 m-phase SHIVs, bearing altered V2 regions, were able to establish spreading infections of cultured alveolar m.

Key Words: immunodeficiency • in situ hybridization • viral load • lymphocyte depletion • HIV env • V2 loop

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