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Home / Equine Research Bank / J Virol / Mapping of equine lentivirus receptor 1 residues critical fo...
Journal of virology2007; 82(3); 1204-1213; doi: 10.1128/JVI.01393-07

Mapping of equine lentivirus receptor 1 residues critical for equine infectious anemia virus envelope binding.

Abstract: The equine lentivirus receptor 1 (ELR1), a member of the tumor necrosis factor receptor (TNFR) protein family, has been identified as a functional receptor for equine infectious anemia virus (EIAV). Toward defining the functional interactions between the EIAV SU protein (gp90) and its ELR1 receptor, we mapped the gp90 binding domain of ELR1 by a combination of binding and functional assays using the EIAV SU gp90 protein and various chimeric receptor proteins derived from exchanges between the functional ELR1 and the nonbinding homolog, mouse herpesvirus entry mediator (murine HveA). Complementary exchanges of the respective cysteine-rich domains (CRD) between the ELR1 and murine HveA proteins revealed CRD1 as the predominant determinant of functional gp90 binding to ELR1 and also to a chimeric murine HveA protein expressed on the surface of transfected Cf2Th cells. Mutations of individual amino acids in the CRD1 segment of ELR1 and murine HveA indicated the Leu70 in CRD1 as essential for functional binding of EIAV gp90 and for virus infection of transduced Cf2Th cells. The specificity of the EIAV SU binding domain identified for the ELR1 receptor is fundamentally identical to that reported previously for functional binding of feline immunodeficiency virus SU to its coreceptor CD134, another TNFR protein. These results indicate unexpected common features of the specific mechanisms by which diverse lentiviruses can employ TNFR proteins as functional receptors.
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Publication Date: 2007-11-21 PubMed ID: 18032504PubMed Central: PMC2224449DOI: 10.1128/JVI.01393-07Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research primarily focuses on studying how the equine infectious anemia virus (EIAV) interacts with its receptor protein in horses, and identifying the specific regions of the receptor that are crucial for this binding process. By analysing and comparing various altered versions of the protein, the researchers could pinpoint certain receptor mutations as key determinants for effective binding and virus infection.

Understanding the interaction between EIAV and its receptor

  • The study is grounded in the understanding of the equine lentivirus receptor 1 (ELR1), which is a functional receptor for EIAV and part of the tumor necrosis factor receptor (TNFR) protein family. The primary binding interaction vital for the EIAV infection process is between the virus’s surface protein, gp90, and ELR1.
  • The researchers mapped out the specific domain of ELR1 necessary for gp90 binding by utilising a mix of binding and functional assays with the EIAV SU gp90 protein. They also used different variations of the protein created from swapping elements between the working ELR1 receptor and a non-binding counterpart in mice, the herpesvirus entry mediator (murine HveA).

Discovering crucial receptor components

  • The team observed the results of interchanging the respective cysteine-rich domains (CRD) between ELR1 and murine HveA proteins. The first domain, CRD1, emerged as the primary influencer in the effective binding of gp90 to ELR1, and to a chimeric murine HveA protein when presented on transfected cells.
  • The researchers identified mutations at the amino acid level in the CRD1 segment of ELR1 and murine HveA. Here, a particular amino acid, Leu70 in CRD1, was found to be essential for effective binding of EIAV gp90 and consequently necessary for the virus to infect cells.

Implications and correlations

  • The precise EIAV SU binding domain identified for ELR1 was found to be fundamentally identical to the feline immunodeficiency virus SU binding with its coreceptor CD134, another protein in the TNFR family. These findings elucidate unexpected common mechanisms between diverse lentiviruses and how they use TNFR proteins as functional receptors.
  • This research expands the understanding of biochemical interactions that allow viral infections in equines, and can contribute to the development of novel interventions or therapies targeting these specific receptor areas.

Cite This Article

APA
Zhang B, Sun C, Jin S, Cascio M, Montelaro RC. (2007). Mapping of equine lentivirus receptor 1 residues critical for equine infectious anemia virus envelope binding. J Virol, 82(3), 1204-1213. https://doi.org/10.1128/JVI.01393-07

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 82
Issue: 3
Pages: 1204-1213

Researcher Affiliations

Zhang, Baoshan
  • Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, W1144 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
Sun, Chengqun
    Jin, Sha
      Cascio, Michael
        Montelaro, Ronald C

          MeSH Terms

          • Amino Acid Sequence
          • Animals
          • Cell Line
          • Dogs
          • Glycoproteins / metabolism
          • Infectious Anemia Virus, Equine / metabolism
          • Mice
          • Molecular Sequence Data
          • Protein Binding
          • Protein Interaction Mapping
          • Receptors, Tumor Necrosis Factor, Member 14 / chemistry
          • Receptors, Tumor Necrosis Factor, Member 14 / genetics
          • Receptors, Tumor Necrosis Factor, Member 14 / metabolism
          • Receptors, Virus / genetics
          • Receptors, Virus / metabolism
          • Viral Envelope Proteins / metabolism
          • Virus Attachment

          Grant Funding

          • R01 CA049296 / NCI NIH HHS
          • R56 AI073261 / NIAID NIH HHS
          • 9R56 AI073261 / NIAID NIH HHS
          • 5R01 CA49296 / NCI NIH HHS

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