Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
Biology of acute infection with macrophage-tropic SIVmac.
Symp Nonhum Primate Models AIDS. 1992 Nov 17-20;10:abstract no. 10. Unique Identifier : AIDSLINE PRIM10/93200940 Ringler D; Mori K; Sasseville V; Walsh D; Pauley D; Hesterberg P; Daniel M; Desrosiers R; Division of Pathology, Harvard Medical School, Southborough, MA.
Abstract:
We previously demonstrated that molecularly-cloned SIVmac239 replicates in lymphoid cells and induces AIDS in rhesus macaques, yet replicates poorly in simian alveolar macrophage cultures. In some SIVmac239-infected animals, macrophage-tropic variants of SIVmac239 arise in vivo and can be isolated from the peripheral blood and/or alveolar macrophages. Genetic analysis of these variants and the use of recombinants and site-specific mutants of SIVmac239 shows that the major genetic determinants responsible for the macrophage tropism are distributed across the full length of env. On the basis of these studies, a molecular clone, called SIVmac239/316Em* (nef open), was constructed which differed from SIVmac239 (nef open) by only eight amino acids in env, but exhibited more than a 100-fold difference in replicative capacity in alveolar macrophages. Both molecularly cloned viruses replicated to high titer in primary lymphocyte cultures. In order to define the in vivo significance of these genetic and functional differences, both viruses were inoculated into rhesus macaques (11 with SIVmac239/316Em* and 8 with SIVmac239) and followed prospectively. Using a limiting dilution PBMC coculture assay and beginning 2 weeks post-inoculation, all 11 animals infected with macrophage-tropic virus had significantly less cell-associated virus in the peripheral blood than did the animals infected with lymphotropic SIV. However, gag antigenemia at 2 weeks postinoculation in the SIVmac239/316Em*-infected animals was either similar to or greater than that in the animals infected with SIVmac239. By 24 weeks post-inoculation, the numbers of CD4+ cells in the blood were lower in the SIVmac239-infected animals. However, SIV-related rash was seen in 9/11 (82%) animals inoculated with macrophage-tropic virus, while rash was only seen in 1/8 (13%) animals infected with SIVmac239. Moreover, in the one animal with rash from the SIVmac239-infected group, a macrophage-tropic variant was isolated from the peripheral blood. In contrast to the relative absence of cells expressing SIV protein or RNA in inflamed skin from animals infected with uncloned SIVmac251, inflamed skin from animals infected with SIVmac239/316Em* contained multiple dermal, and rare epidermal, mononuclear cells immunoreactive for SIV protein. These results suggest that, similar to SIV encephalitis and granulomatous pneumonia, SIV-related rash arises as a consequence of infection of tissue macrophages. The basis for reduced PBMC-associated viral loads in animals infected with macrophage-tropic virus will require further investigation.
Keywords: Animal Comparative Study Genes, env Genes, gag Genes, nef Lymphocytes/MICROBIOLOGY Macaca mulatta Macrophages/*MICROBIOLOGY Macrophages, Alveolar/*MICROBIOLOGY Recombination, Genetic Simian Acquired Immunodeficiency Syndrome/BLOOD/IMMUNOLOGY/ *MICROBIOLOGY SIV/GENETICS/ISOLATION & PURIF/*PHYSIOLOGY Variation (Genetics) *Virus Replication ABSTRACT 930630
M9361080
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Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
