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Transferrin Receptor Protein 1 Cooperates with mGluR2 To Mediate the Internalization of Rabies Virus and SARS-CoV-2

Xinxin Wang1, Zhiyuan Wen1, Huizhen Cao1

  • 1State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.

Journal of Virology
|February 13, 2023
PubMed

Insights

Metabotropic glutamate receptor subtype 2 (mGluR2) and transferrin receptor 1 (TfR1) form a novel axis essential for Rabies virus (RABV) and SARS-CoV-2 entry. Targeting this mGluR2-TfR1 axis offers new therapeutic strategies against these viral infections.

Area of Science:

  • Virology
  • Cell Biology
  • Neuroscience

Background:

  • Identifying viral entry receptors is crucial for developing therapeutics against Rabies virus (RABV) and SARS-CoV-2.
  • Metabotropic glutamate receptor subtype 2 (mGluR2) was previously suggested as an entry factor for RABV and an internalization factor for SARS-CoV-2.

Purpose of the Study:

  • To demonstrate the role of mGluR2 in RABV infection in vivo.
  • To elucidate the mechanism of mGluR2-mediated viral entry for both RABV and SARS-CoV-2.
  • To identify potential therapeutic targets for RABV and SARS-CoV-2.

Main Methods:

  • In vitro and in vivo experiments using mGluR2 and transferrin receptor 1 (TfR1) knockdown models.
  • Co-immunoprecipitation assays to study protein interactions.
  • Analysis of viral internalization and infection in the presence and absence of mGluR2 and TfR1.

Main Results:

  • mGluR2 facilitates RABV internalization in vitro and infection in vivo; mGluR2 gene knockout mice survived RABV challenge.
  • TfR1 interacts with mGluR2 and is essential for mGluR2-mediated endocytosis of RABV.
  • TfR1 also interacts with the SARS-CoV-2 spike protein and is critical for SARS-CoV-2 internalization.

Conclusions:

  • A novel mGluR2-TfR1 axis is identified as a critical pathway for RABV and SARS-CoV-2 entry.
  • TfR1 cooperates with mGluR2 to regulate the endocytosis of both viruses.
  • The mGluR2-TfR1 axis represents a promising therapeutic target for combating RABV and SARS-CoV-2 infections.
Keywords:
SARS-CoV-2TfR1internalizationmGluR2rabies virus

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