Binding of equine infectious anemia virus to the equine lentivirus receptor-1 is mediated by complex discontinuous sequences in the viral envelope gp90 protein.
Abstract: The identification and characterization of a functional cellular receptor for equine infectious anemia virus (EIAV), designated equine lentivirus receptor-1 (ELR1), a member of the tumour necrosis factor receptor protein family, has been reported previously [Zhang, B. et al. (2005). Proc Natl Acad Sci U S A, 102 , 9918-9923]. The finding of a single receptor for EIAV is distinct from feline, simian and human immunodeficiency viruses, which typically utilize two co-receptors for infection, but is similar to avian and murine oncoviruses, which use single receptors. This study sought to determine ELR1-binding domains of EIAV gp90. Towards this goal, a GFP-tagged gp90 fusion protein (gp90GFP) expression vector was constructed and a specific cell-cell binding assay was developed to measure EIAV gp90 binding to ELR1. Using these assays, the receptor-binding properties of 41 gp90GFP mutants were evaluated, each with a sequential replacement 11 aa linear epitope peptide from the vesicular stomatitis virus glycoprotein (VSV-G tag), as well as eight mutants containing individual gp90 variable-domain deletions. The results of these studies demonstrated that, in general, gp90 constructs containing substitutions or deletions in the N-terminal third of gp90 retained their receptor-binding activity. In contrast, segment substitutions or deletions in the C-terminal two-thirds of gp90 eliminated receptor-binding activity. Thus, these results reveal for the first time that the ELR1-binding domains of EIAV gp90 are located in the C-terminal two-thirds of EIAV gp90, apparently as a complex of discontinuous determinants.
Publication Date: 2008-07-18 PubMed ID: 18632973DOI: 10.1099/vir.0.83646-0Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- N.I.H.
- Extramural
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.
This study examines how equine infectious anemia virus (EIAV) latches onto its receptor, ELR1, on horse cells. The interaction is controlled by a intricate sequence in a viral protein, gp90. Clarifying the binding details may further our understanding of the virus and help in drug development.
Background
- The research is about understanding how equine infectious anemia virus (EIAV) binds with its receptor ELR1 on horse cells. This process is crucial in virus spread and infection.
- ELR1 is a member of the tumour necrosis factor receptor protein family. The interaction between EIAV and ELR1 is distinct and simpler than some other viruses as it involves a single receptor, rather than two co-receptors like in feline, simian, and human immunodeficiency viruses.
Objective and Methodology
- The objective was to discover the specific regions of the EIAV gp90 protein that are responsible for binding with ELR1.
- The researchers built a special fluorescently labeled gp90 protein (gp90GFP), and a cell-cell binding assay to measure its interaction with ELR1.
- A wide range of gp90GFP mutants were produced to identify the regions critical for receptor binding. Each variant featured a different 11 aa linear epitope peptide from the vesicular stomatitis virus glycoprotein (VSV-G tag) swapped into the gp90 protein.
Results
- The experiments revealed that substitutions or removals in the initial third of the gp90 protein did not affect its ability to bind with ELR1.
- While alterations in the C-terminal two-thirds (later part) of gp90 resulted in the loss of receptor-binding activity. Hence, it was concluded that the receptor-binding regions of EIAV gp90 are located in the C-terminal two-thirds.
- The research shows that virus-receptor binding isn’t a result of simple and continuous interaction, but it involves complex discontinuous determinants spread over the gp90 protein.
Conclusion
- This study has provided new insights into the EIAV binding process, which is crucial for understanding the viral infection mechanism and could subsequently guide the development of therapeutic strategies.
Cite This Article
APA
Sun C, Zhang B, Jin J, Montelaro RC.
(2008).
Binding of equine infectious anemia virus to the equine lentivirus receptor-1 is mediated by complex discontinuous sequences in the viral envelope gp90 protein.
J Gen Virol, 89(Pt 8), 2011-2019.
https://doi.org/10.1099/vir.0.83646-0 Publication
Researcher Affiliations
- Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
- Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
- Department of Infectious Disease and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
- Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
- Department of Infectious Disease and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
- Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
MeSH Terms
- Amino Acid Sequence
- Animals
- Cell Line
- Flow Cytometry
- Glycoproteins / chemistry
- Glycoproteins / genetics
- Glycoproteins / metabolism
- Green Fluorescent Proteins / genetics
- Green Fluorescent Proteins / metabolism
- Humans
- Infectious Anemia Virus, Equine / metabolism
- Molecular Sequence Data
- Mutation
- Protein Binding
- Receptors, Tumor Necrosis Factor / metabolism
- Receptors, Tumor Necrosis Factor, Member 14
- Receptors, Virus / metabolism
- Recombinant Fusion Proteins / genetics
- Recombinant Fusion Proteins / metabolism
- Sequence Deletion
- Transfection
- Viral Envelope Proteins / chemistry
- Viral Envelope Proteins / genetics
- Viral Envelope Proteins / metabolism
- Virus Attachment
Grant Funding
- 5R01 CA49296 / NCI NIH HHS
- 9R56 AI073261 / NIAID NIH HHS
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
