Cargando…

Molecular characterization of HIV-1 genome in fission yeast Schizosaccharomyces pombe

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)...

Descripción completa

Detalles Bibliográficos
Autores principales: Nkeze, Joseph, Li, Lin, Benko, Zsigmond, Li, Ge, Zhao, Richard Y
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549081/
https://www.ncbi.nlm.nih.gov/pubmed/26309721
http://dx.doi.org/10.1186/s13578-015-0037-7
_version_ 1782387265378451456
author Nkeze, Joseph
Li, Lin
Benko, Zsigmond
Li, Ge
Zhao, Richard Y
author_facet Nkeze, Joseph
Li, Lin
Benko, Zsigmond
Li, Ge
Zhao, Richard Y
author_sort Nkeze, Joseph
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4549081
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-45490812015-08-26 Molecular characterization of HIV-1 genome in fission yeast Schizosaccharomyces pombe Nkeze, Joseph Li, Lin Benko, Zsigmond Li, Ge Zhao, Richard Y Cell Biosci Research 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. BioMed Central 2015-08-25 /pmc/articles/PMC4549081/ /pubmed/26309721 http://dx.doi.org/10.1186/s13578-015-0037-7 Text en © Nkeze et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Nkeze, Joseph
Li, Lin
Benko, Zsigmond
Li, Ge
Zhao, Richard Y
Molecular characterization of HIV-1 genome in fission yeast Schizosaccharomyces pombe
title Molecular characterization of HIV-1 genome in fission yeast Schizosaccharomyces pombe
title_full Molecular characterization of HIV-1 genome in fission yeast Schizosaccharomyces pombe
title_fullStr Molecular characterization of HIV-1 genome in fission yeast Schizosaccharomyces pombe
title_full_unstemmed Molecular characterization of HIV-1 genome in fission yeast Schizosaccharomyces pombe
title_short Molecular characterization of HIV-1 genome in fission yeast Schizosaccharomyces pombe
title_sort molecular characterization of hiv-1 genome in fission yeast schizosaccharomyces pombe
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549081/
https://www.ncbi.nlm.nih.gov/pubmed/26309721
http://dx.doi.org/10.1186/s13578-015-0037-7
work_keys_str_mv AT nkezejoseph molecularcharacterizationofhiv1genomeinfissionyeastschizosaccharomycespombe
AT lilin molecularcharacterizationofhiv1genomeinfissionyeastschizosaccharomycespombe
AT benkozsigmond molecularcharacterizationofhiv1genomeinfissionyeastschizosaccharomycespombe
AT lige molecularcharacterizationofhiv1genomeinfissionyeastschizosaccharomycespombe
AT zhaorichardy molecularcharacterizationofhiv1genomeinfissionyeastschizosaccharomycespombe