title: Molecular characterization of HIV-1 genome in fission yeast Schizosaccharomyces pombe.
abstract: BACKGROUND
  The human immunodeficiency virus type 1 (HIV-1) genome (~9 kb RNA) is flanked by two long terminal repeats (LTR) promoter regions with nine open reading frames, which encode Gag, Pol and Env polyproteins, four accessory proteins (Vpu, Vif, Vpr, Nef) and two regulatory proteins (Rev, Tat). In this study, we carried out a genome-wide and functional analysis of the HIV-1 genome in fission yeast (Schizosaccharomyces pombe).
  
  
  RESULTS
  Each one of the HIV-1 genes was cloned and expressed individually in fission yeast. Subcellular localization of each viral protein was first examined. The effect of protein expression on cellular proliferation and colony formations, an indication of cytotoxicity, were observed. Overall, there is a general correlation of subcellular localization of each viral protein between fission yeast and mammalian cells. Three viral proteins, viral protein R (Vpr), protease (PR) and regulator of expression of viral protein (Rev), were found to inhibit cellular proliferation. Rev was chosen for further analysis in fission yeast and mammalian cells. Consistent with the observation in fission yeast, expression of HIV-1 rev gene also caused growth retardation in mammalian cells. However, the observed growth delay was neither due to the cytotoxic effect nor due to alterations in cell cycling. Mechanistic testing of the Rev effect suggests it triggers transient induction of cellular oxidative stress.
  
  
  CONCLUSIONS
  Some of the behavioral and functional similarities of Rev between fission yeast and mammalian cells suggest fission yeast might be a useful model system for further studies of molecular functions of Rev and other HIV-1 viral proteins.
authors: Division of Molecular Pathology, Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201-1192 USA.
authors: Joseph
authors: J
authors: Nkeze
authors: Division of Molecular Pathology, Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201-1192 USA.|AIDS Research Department, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071 China.
authors: Lin
authors: L
authors: Li
authors: Division of Molecular Pathology, Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201-1192 USA.|Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria.
authors: Zsigmond
authors: Z
authors: Benko
authors: Division of Molecular Pathology, Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201-1192 USA.
authors: Ge
authors: G
authors: Li
authors: Division of Molecular Pathology, Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201-1192 USA.|Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201-1192 USA.|Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201-1192 USA.
authors: Richard Y
authors: RY
authors: Zhao
keywords: Cellular proliferation; Colony formation; Fission yeast; Functional analysis; Gene expression; HIV-1; Mammalian cell; Oxidative stress; Schizosaccharomyces pombe; Subcellular localization; Viral genome