Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
Construction and in vitro properties of SIVmac mutants with deletions in nonessential genes [corrected and republished article originally printed in AIDS Res Hum Retroviruses 1994 Apr;10(4):333-42]
AIDS Res Hum Retroviruses. 1994 May;10(5):607-16. Unique Identifier : AIDSLINE MED/95000934 Gibbs JS; Regier DA; Desrosiers RC; Harvard Medical School, New England Regional Primate Research; Center, Southborough, Massachusetts 01772-9102.
Abstract:
The so-called nonessential genes of primate lentiviruses can be deleted without abrogating the ability of virus to replicate under at least some cell culture conditions. In SIVmac, these genes are vif, vpx, vpr, and nef. Sequences in the upstream region of U3 in the LTR have also been shown to be dispensable for replication in cell culture. We report here the construction and characterization of a panel of 40 single and combination deletion mutants derived from the pathogenic molecular clone SIVmac239. Deletion of the vpr gene caused little or no change in the growth properties of SIVmac239 in CEMx174 cells, in rhesus monkey peripheral blood mononuclear cells (PBMCs), or in rhesus monkey alveolar macrophages. Deletion of the vpx gene resulted in a greatly reduced rate of replication of the virus in the primary PBMC and macrophage cultures, but no significant reduction in replication of the virus in CEMx174 cells. Deletion of the vpx gene appeared to have a greater effect on virus replication in macrophages than in PBMCs. Deletion of the vif gene caused a dramatic reduction in replication in all cell types tested. However, even delta 5, which contains deletions in all five targeted regions (vif, vpx, vpr, nef, and U3), can still replicate in CEMx174 cells albeit with greatly delayed kinetics. Deletion of nef, alone or in combination with deletions in U3 and vpr, had no observable effect on replication of the virus in any of the cells tested. Because the disease induced by the parental SIVmac239 clone in rhesus monkeys has been well characterized and is remarkably similar to AIDS in humans, this collection of mutants will be useful for relating in vitro properties and gene function with in vivo pathogenic potential.
Keywords: Amino Acid Sequence Animal Base Sequence Cell Line DNA Primers/GENETICS DNA, Viral/GENETICS Gene Products, env/*GENETICS Genes, nef Genes, vif Genes, vpr Genes, vpu *Genes, Viral Leukocytes, Mononuclear/MICROBIOLOGY Macaca mulatta Macrophages, Alveolar/MICROBIOLOGY Molecular Sequence Data Mutagenesis Retroviridae Proteins, Oncogenic/*GENETICS *Sequence Deletion Support, U.S. Gov't, P.H.S. SIV/*GENETICS/PHYSIOLOGY Viral Fusion Proteins/*GENETICS Virus Replication/GENETICS CORRECTED AND REPUBLISHED ARTICLE JOURNAL ARTICLE 950130
M9510837
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Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
