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

Nkeze J, Li L, Benko Z, Li G, Zhao RY - Cell Biosci (2015)

Bottom Line: Three viral proteins, viral protein R (Vpr), protease (PR) and regulator of expression of viral protein (Rev), were found to inhibit cellular proliferation.Mechanistic testing of the Rev effect suggests it triggers transient induction of cellular oxidative stress.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Pathology, Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201-1192 USA.

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.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of HIV-1 genome. The total size of HIV-1 genome is approximately 9.7 kb. Each of the viral genes is drawing based on the relative orientation in the entire RNA genome. Arrows points to cleaved protein products. Dashed lines represent RNA splicing. The number in parenthesis is molecular weight of each protein. LTR long-term repeat, Gag group-specific antigen, MA matrix protein, CA capsid domain, NC nucleocapsid, TF trans-frame protein, Pol polymerases, PR protease, RT reverse transcriptase, IN integrase, Env envelope protein, SU surface membrane protein, TM trans-membrane protein, Vif viral infectivity factor, Vpr viral protein R, Vpu viral protein U, Nef negative regulatory factor, Rev regulator of expression of viral proteins, Tat trans-activator of transcription.
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Fig1: Schematic diagram of HIV-1 genome. The total size of HIV-1 genome is approximately 9.7 kb. Each of the viral genes is drawing based on the relative orientation in the entire RNA genome. Arrows points to cleaved protein products. Dashed lines represent RNA splicing. The number in parenthesis is molecular weight of each protein. LTR long-term repeat, Gag group-specific antigen, MA matrix protein, CA capsid domain, NC nucleocapsid, TF trans-frame protein, Pol polymerases, PR protease, RT reverse transcriptase, IN integrase, Env envelope protein, SU surface membrane protein, TM trans-membrane protein, Vif viral infectivity factor, Vpr viral protein R, Vpu viral protein U, Nef negative regulatory factor, Rev regulator of expression of viral proteins, Tat trans-activator of transcription.

Mentions: The human immunodeficiency virus type 1 (HIV-1), like other retroviruses, is made up of an RNA encoded genome of approximately 9.7 kilobases (kb). Both ends of the RNA genome are flanked by a long terminal repeat (LTR) promoter region (Fig. 1). Between the two LTR regions, there are three polyproteins (Gag, Pol, Env), four accessory proteins (Vpu, Vif, Vpr, Nef) and two regulatory proteins (Rev, Tat). HIV-1 RNA also contains regulatory regions which are important for transcription initiation and polyadenylation.Fig. 1


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

Nkeze J, Li L, Benko Z, Li G, Zhao RY - Cell Biosci (2015)

Schematic diagram of HIV-1 genome. The total size of HIV-1 genome is approximately 9.7 kb. Each of the viral genes is drawing based on the relative orientation in the entire RNA genome. Arrows points to cleaved protein products. Dashed lines represent RNA splicing. The number in parenthesis is molecular weight of each protein. LTR long-term repeat, Gag group-specific antigen, MA matrix protein, CA capsid domain, NC nucleocapsid, TF trans-frame protein, Pol polymerases, PR protease, RT reverse transcriptase, IN integrase, Env envelope protein, SU surface membrane protein, TM trans-membrane protein, Vif viral infectivity factor, Vpr viral protein R, Vpu viral protein U, Nef negative regulatory factor, Rev regulator of expression of viral proteins, Tat trans-activator of transcription.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4549081&req=5

Fig1: Schematic diagram of HIV-1 genome. The total size of HIV-1 genome is approximately 9.7 kb. Each of the viral genes is drawing based on the relative orientation in the entire RNA genome. Arrows points to cleaved protein products. Dashed lines represent RNA splicing. The number in parenthesis is molecular weight of each protein. LTR long-term repeat, Gag group-specific antigen, MA matrix protein, CA capsid domain, NC nucleocapsid, TF trans-frame protein, Pol polymerases, PR protease, RT reverse transcriptase, IN integrase, Env envelope protein, SU surface membrane protein, TM trans-membrane protein, Vif viral infectivity factor, Vpr viral protein R, Vpu viral protein U, Nef negative regulatory factor, Rev regulator of expression of viral proteins, Tat trans-activator of transcription.
Mentions: The human immunodeficiency virus type 1 (HIV-1), like other retroviruses, is made up of an RNA encoded genome of approximately 9.7 kilobases (kb). Both ends of the RNA genome are flanked by a long terminal repeat (LTR) promoter region (Fig. 1). Between the two LTR regions, there are three polyproteins (Gag, Pol, Env), four accessory proteins (Vpu, Vif, Vpr, Nef) and two regulatory proteins (Rev, Tat). HIV-1 RNA also contains regulatory regions which are important for transcription initiation and polyadenylation.Fig. 1

Bottom Line: Three viral proteins, viral protein R (Vpr), protease (PR) and regulator of expression of viral protein (Rev), were found to inhibit cellular proliferation.Mechanistic testing of the Rev effect suggests it triggers transient induction of cellular oxidative stress.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Pathology, Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201-1192 USA.

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.

No MeSH data available.


Related in: MedlinePlus