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Proceedings of the National Academy of Sciences of the United States of America2005; 102(28); 9918-9923; doi: 10.1073/pnas.0501560102

A tumor necrosis factor receptor family protein serves as a cellular receptor for the macrophage-tropic equine lentivirus.

Abstract: Characterization of cellular receptors for human, simian, and feline immunodeficiency viruses that are tropic for lymphocytes and macrophages have revealed a common theme of a sequential binding of viral envelope proteins with two coreceptors to mediate virus infection of target cells. In contrast to these dual tropic immunodeficiency viruses, the ungulate lentiviruses, including equine infectious anemia virus (EIAV), exclusively infect cells of the monocyte-macrophage lineage to cause progressive degenerative diseases without clinical immunodeficiency. EIAV causes a uniquely dynamic disease that is characterized by recurrent disease episodes including fever, diarrhea, lethargy, anemia, and thrombocytopenia. Although EIAV provides an important animal model for lentivirus disease resulting from macrophage infection, to date there has been no definition of the specific cellular receptor(s) used by the equine lentivirus to infect target cells. In the current study, we have identified and cloned a functional receptor for EIAV, designated equine lentivirus receptor-1 (ELR1), related to the family of TNF receptor (TNFR) proteins. ELR1 was shown to be expressed in various equine cells permissive for EIAV replication in vitro, including monocytes and macrophages. In contrast, EIAV-resistant human, murine, and simian cells were negative for ELR1 expression but became susceptible to virus infection when transduced with a recombinant murine retrovirus expressing the ELR1. Thus, these results identify a specific functional receptor for a macrophagetropic lentivirus and indicate that infection by EIAV may be mediated by a single receptor, in contrast to coreceptors used by the lymphotropic immunodeficiency lentiviruses.
Publication Date: 2005-06-28 PubMed ID: 15985554PubMed Central: PMC1174982DOI: 10.1073/pnas.0501560102Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • U.S. Gov't
  • P.H.S.

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 study focuses on unraveling the specific cellular receptor used by the macrophage-tropic equine lentivirus (equine infectious anemia virus or EIAV) to infect target cells. The research identifies a functional virus receptor known as equine lentivirus receptor-1 (ELR1), belonging to the tumor necrosis factor receptor (TNFR) family of proteins.

Background

  • The study starts by comparing the process of virus infection by human, simian, and feline immunodeficiency viruses and the equine infectious anemia virus (EIAV). The former viruses use a sequential binding process with two coreceptors to infect target cells.
  • The EIAV is identified as a lentivirus that mostly infects cells of the monocyte-macrophage lineage leading to progressive degenerative diseases devoid of clinical immunodeficiency.
  • Notably, EIAV’s disease progression is dynamic, chronic, and is characterized by recurring disease episodes such as fever, diarrhea, lethargy, anemia, and thrombocytopenia.

Findings

  • Researchers identified and cloned the equine lentivirus receptor-1 (ELR1), which serves as the functional receptor for EIAV. This receptor belongs to the tumor necrosis factor receptor (TNFR) family of proteins.
  • The expression of ELR1 was tested and confirmed in various equine cells that are permissive for EIAV replication such as monocytes and macrophages.
  • Additionally, human, murine, and simian cells that resisted EIAV were found not to express the ELR1 receptor. However, these cells became vulnerable to the virus infection when they were transduced with a recombinant murine retrovirus expressing the ELR1 receptor. This signifies the specificity of ELR1 receptor for EIAV infection.

Conclusions

  • The study concludes that the EIAV uses a specific functional receptor, ELR1, to infect its target cells. This contrasts other immunodeficiency lentiviruses which use coreceptors for infection.
  • These findings offer crucial insights into the understanding of how EIAV infects and progresses in its host organism, providing a basis for further studies into the development of effective interventions and treatments.

Cite This Article

APA
Zhang B, Jin S, Jin J, Li F, Montelaro RC. (2005). A tumor necrosis factor receptor family protein serves as a cellular receptor for the macrophage-tropic equine lentivirus. Proc Natl Acad Sci U S A, 102(28), 9918-9923. https://doi.org/10.1073/pnas.0501560102

Publication

ISSN: 0027-8424
NlmUniqueID: 7505876
Country: United States
Language: English
Volume: 102
Issue: 28
Pages: 9918-9923

Researcher Affiliations

Zhang, Baoshan
  • Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Jin, Sha
    Jin, Jing
      Li, Feng
        Montelaro, Ronald C

          MeSH Terms

          • Amino Acid Sequence
          • Animals
          • Base Sequence
          • Cell Line
          • Cloning, Molecular
          • DNA Primers
          • DNA, Complementary / genetics
          • Genetic Vectors
          • Humans
          • Infectious Anemia Virus, Equine / metabolism
          • Macrophages / metabolism
          • Molecular Sequence Data
          • Receptors, Tumor Necrosis Factor / genetics
          • Receptors, Tumor Necrosis Factor / metabolism
          • Retroviridae
          • Reverse Transcriptase Polymerase Chain Reaction
          • Sequence Analysis, DNA
          • Transfection
          • Viral Envelope Proteins / metabolism

          Grant Funding

          • R01 CA049296 / NCI NIH HHS
          • 5R01 CA 49296 / NCI NIH HHS

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