Article: article from journal or magazin.
Analysis of natural variants of the human immunodeficiency virus type 1 gag-pol frameshift stem-loop structure.
Journal of virology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Human immunodeficiency virus type 1 uses ribosomal frameshifting for translation of the Gag-Pol polyprotein. Frameshift activities are thought to be tightly regulated. Analysis of gag p1 sequences from 270 plasma virions identified in 64% of the samples the occurrence of polymorphism that could lead to changes in thermodynamic stability of the stem-loop. Expression in Saccharomyces cerevisiae of p1-beta-galactosidase fusion proteins from 10 representative natural stem-loop variants and three laboratory mutant constructs (predicted the thermodynamic stability [Delta G degrees] ranging from -23.0 to -4.3 kcal/mol) identified a reduction in frameshift activity of 13 to 67% compared with constructs with the wild-type stem-loop (Delta G degrees, -23.5 kcal/mol). Viruses carrying stem-loops associated with greater than 60% reductions in frameshift activity presented profound defects in viral replication. In contrast, viruses with stem-loop structures associated with 16 to 42% reductions in frameshift efficiency displayed no significant viral replication deficit.
Base Sequence, Frameshifting, Ribosomal, Genes, gag, Genes, pol, Genetic Variation, HIV-1, Humans, Leukocytes, Mononuclear, Molecular Sequence Data, Mutagenesis, Site-Directed, Nucleic Acid Conformation, Thermodynamics, Virion, Virus Replication
Web of science
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