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

Abstract

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 (mφ) 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 mφ-phase SHIVs, bearing altered V2 regions, were able to establish spreading infections of cultured alveolar mφ.