Cell Tropism of Simian Immunodeficiency Virus in Culture Is Not Predictive of in VivoTropism or Pathogenesis

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Title: Cell Tropism of Simian Immunodeficiency Virus in Culture Is Not Predictive of in VivoTropism or Pathogenesis
Authors: Borda, Juan T., Alvarez, Xavier, Kondova, Ivanela, Aye, Pyone, Simon, Meredith A., Desrosiers, Ronald C., Lackner, Andrew A.
Source: American Journal of Pathology; December 2004, Vol. 165 Issue: 6 p2111-2122, 12p
Abstract: SIVmac239/316 is a molecular clone derived from SIVmac239 that differs from the parental virus by nine amino acids in env. This virus, unlike the parental SIVmac239, is able to replicate well in alveolar macrophages in culture. We have not however, observed macrophage-associated inflammatory disease in any animal infected with SIVmac239/316. Therefore, we sought to examine the cell tropism of this virus in vivoin multiple tissues using in situhybridization combined with immunohistochemistry and multilabel confocal microscopy for viral nucleic acid and multiple cell-type-specific markers for macrophages and T lymphocytes. Tissues examined included brain, heart, lung, lymph nodes, spleen, thymus, and small and large intestine. Matched tissues from macaques infected with the parental SIVmac239 and uninfected macaques were also examined. Many infected cells were detected in the tissues of animals infected with SIVmac239 and SIVmac239/316 although there appeared to be fewer positive cells in animals infected with SIVmac239/316. Surprisingly, in light of the cell culture observations, nearly every simian immunodeficiency virus-infected cell in animals inoculated with SIVmac239/316 was a T lymphocyte rather than a macrophage. This was true both during early infection (first 2 months) and in terminal disease. In contrast, as previously described, SIVmac239 was found in both T cells and macrophages in tissues as early as 21 days after infection. These studies indicate that during both acute and chronic SIVmac239/316 infection T lymphocytes rather than macrophages are the principal targets in vivo. These data combined with the absence of macrophage-associated lesions in SIVmac239/316-infected animals indicate that in vitrocell tropism is not predictive of in vivotropism or disease pathogenesis.
Database: Supplemental Index
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ISSN:00029440
DOI:10.1016/S0002-9440(10)63261-0
Published in:American Journal of Pathology
Language:English