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Home / Equine Research Bank / PLoS One / Structural model of the Rev regulatory protein from equine i...
PloS one2009; 4(1); e4178; doi: 10.1371/journal.pone.0004178

Structural model of the Rev regulatory protein from equine infectious anemia virus.

Abstract: Rev is an essential regulatory protein in the equine infectious anemia virus (EIAV) and other lentiviruses, including HIV-1. It binds incompletely spliced viral mRNAs and shuttles them from the nucleus to the cytoplasm, a critical prerequisite for the production of viral structural proteins and genomic RNA. Despite its important role in production of infectious virus, the development of antiviral therapies directed against Rev has been hampered by the lack of an experimentally-determined structure of the full length protein. We have used a combined computational and biochemical approach to generate and evaluate a structural model of the Rev protein. The modeled EIAV Rev (ERev) structure includes a total of 6 helices, four of which form an anti-parallel four-helix bundle. The first helix contains the leucine-rich nuclear export signal (NES). An arginine-rich RNA binding motif, RRDRW, is located in a solvent-exposed loop region. An ERLE motif required for Rev activity is predicted to be buried in the core of modeled structure where it plays an essential role in stabilization of the Rev fold. This structural model is supported by existing genetic and functional data as well as by targeted mutagenesis of residues predicted to be essential for overall structural integrity. Our predicted structure should increase understanding of structure-function relationships in Rev and may provide a basis for the design of new therapies for lentiviral diseases.
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Publication Date: 2009-01-12 PubMed ID: 19137065PubMed Central: PMC2613556DOI: 10.1371/journal.pone.0004178Google Scholar: Lookup
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Summary

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The research focuses on the development of a structural model for the Rev regulatory protein found in the equine infectious anemia virus (EIAV) and other similar viruses using a combined computational and biochemical approach. This model could help to enhance understanding of the protein’s functionality and may form the base for designing new therapeutic strategies for lentiviral diseases.

Introduction to Rev Protein and Its Importance

  • The Rev protein is a crucial regulatory element in the EIAV and other lentiviruses, which include HIV-1.
  • It functions by binding to viral mRNAs that are not completely spliced and subsequently transfers them from the nucleus to the cytoplasm.
  • This process is a critical prerequisite for the production of viral structural proteins and genomic RNA, essential components in creating an infectious virus.
  • Despite Rev’s fundamental role in virus formation, the creation of antiviral treatments focused on it has been hindered due to the absence of a full-length protein structure determined through experimentation.

Development of the Rev Protein’s Structural Model

  • In this study, researchers have used a joint computational and biochemical approach to create and analyze a structural model of the Rev protein.
  • The model of the EIAV Rev (ERev) is comprised of a total of 6 helices, with four of them forming an anti-parallel four-helix bundle.
  • The first helix holds the leucine-rich nuclear export signal (NES), while a solvent-exposed loop region carries an arginine-rich RNA binding motif, RRDRW.
  • An ERLE motif, crucial for Rev’s activity, is predicted to be tucked away in the modeled structure’s core, where it plays a vital role in stabilizing the Rev fold.

Validation and Potential Application of the Model

  • The validity of the constructed model is supported by existing genetic and functional data, as well as targeted mutagenesis of residues thought to be necessary for maintaining the overall structural integrity.
  • This predicted structure is hoped to enhance understanding of the structure-function relationships in the Rev protein.
  • The study results may contribute to the creation of innovative therapies for lentiviral diseases, potentially paving new ways for therapeutic interventions in HIV and other similar infections.

Cite This Article

APA
Ihm Y, Sparks WO, Lee JH, Cao H, Carpenter S, Wang CZ, Ho KM, Dobbs D. (2009). Structural model of the Rev regulatory protein from equine infectious anemia virus. PLoS One, 4(1), e4178. https://doi.org/10.1371/journal.pone.0004178

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 4
Issue: 1
Pages: e4178
PII: e4178

Researcher Affiliations

Ihm, Yungok
  • Department of Physics and Astronomy, Iowa State University, Ames, IA, USA. yihm@spring8.or.jp
Sparks, Wendy O
    Lee, Jae-Hyung
      Cao, Haibo
        Carpenter, Susan
          Wang, Cai-Zhuang
            Ho, Kai-Ming
              Dobbs, Drena

                MeSH Terms

                • Amino Acid Sequence
                • Animals
                • Binding Sites
                • Gene Products, rev / chemistry
                • Gene Products, rev / genetics
                • Gene Products, rev / metabolism
                • Horse Diseases
                • Horses / microbiology
                • Infectious Anemia Virus, Equine / chemistry
                • Infectious Anemia Virus, Equine / genetics
                • Infectious Anemia Virus, Equine / metabolism
                • Models, Structural
                • Molecular Sequence Data
                • Mutagenesis
                • Protein Structure, Tertiary / genetics
                • Structure-Activity Relationship

                Grant Funding

                • R01 CA128568 / NCI NIH HHS
                • R21 CA097936 / NCI NIH HHS
                • CA97936 / NCI NIH HHS

                Conflict of Interest Statement

                The authors have declared that no competing interests exist.

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                Citations

                This article has been cited 4 times.
                1. Zhang X, Li J, Zhang M, Bai B, Ma W, Lin Y, Guo X, Wang XF, Wang X. A Novel, Fully Spliced, Accessory Gene in Equine Lentivirus with Distinct Rev-Responsive Element.. J Virol 2022 Sep 28;96(18):e0098622.
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