A Block to Efficient Replication of Simian Immunodeficiency Virus in C8166 Cells Can Be Overcome by Duplication of the NF-kappaB Binding Site.

Abstract

Sequence analysis of the acutely lethal pbj14 strain of simian immunodeficiency virus (SIVpbj14) clone revealed among other differences from its less pathogenic counterparts a duplication of its binding site for nuclear factor kappa B (NF-kappaB) in its long terminal repeats (LTR). We have investigated whether introducing a similar duplication into the pathogenic molecular clone SIV mac239 would alter its biological properties. We compared an SIV which possessed 2 NF-kappaB sites to the wild type, a single NF-kappaB site virus, with respect to its ability to replicate in vitro in established CD4+ T cell lines, primary peripheral blood mononuclear cells (PBMCs), and primary alveolar macrophages. The virus containing 2 NF-kappaB sites exhibited no apparent difference from wild type in established cell lines 174xCEM, MT-2 and MT-4, or in primary PBMC or tissue macrophage cultures. However, the 2 kappaB virus replicated well in the established cell line C8166, while the wild type, 1 kappaB virus replicated very poorly in this cell type, suggesting that duplication of the NF-kappaB site is capable of overcoming a block to efficient replication of SIVmac239 in C8166 cells. Interestingly, Em*, a macrophage tropic SIVmac that differs from SIVmac239 by 9 amino acids in the envelope region yet possesses only one NK-kappaB binding sites, also replicates well in C8166. The data suggest that the replication of wild type SIVmac239 is restricted in C8166 cells, but that this restriction can be overcome either by changes in the LTR or by changes in the envelope region. Copyright 1996 S. Karger AG, Basel