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CD164 is a host factor for lymphocytic choriomeningitis virus entry

Mark J G Bakkers1, Alex Moon-Walker1,2,3,4, Rasmus Herlo5

  • 1Department of Microbiology, Harvard Medical School, Boston, MA 02115.

Proceedings of the National Academy of Sciences of the United States of America
|March 2, 2022
PubMed

Insights

Lymphocytic choriomeningitis virus (LCMV) uses host cell factors, including CD164 and alpha-dystroglycan (α-DG), for entry. The virus switches receptors during entry, offering new therapeutic targets.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Lymphocytic choriomeningitis virus (LCMV) is a zoonotic arenavirus transmitted by rodents.
  • LCMV infection can lead to severe congenital abnormalities and is a significant risk for transplant recipients.

Purpose of the Study:

  • To identify host factors essential for LCMV entry into host cells.
  • To elucidate the mechanism of LCMV cell entry and identify potential therapeutic targets.

Main Methods:

  • Genome-wide loss-of-function screen to identify host factors.
  • Biochemical analysis of LCMV glycoprotein interactions.
  • Cellular entry pathway analysis.

Main Results:

  • Identified CD164, glycosylation factors, heparan sulfate machinery, and alpha-dystroglycan (α-DG) as host factors for LCMV entry.
  • LCMV glycoprotein binds CD164 at acidic pH, requiring a sialylated glycan.
  • LCMV entry involves a switch from initial binding (heparan sulfate or α-DG) to CD164 before membrane fusion.

Conclusions:

  • CD164 is a novel, critical host factor for LCMV cell entry.
  • The identified host factors and entry mechanism provide new targets for antiviral therapies against LCMV.
Keywords:
CD164arenaviruslymphocytic choriomeningitis virusvirus entry

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