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Myeloid-associated differentiation marker is an essential host factor for human parechovirus PeV-A3 entry

Kanako Watanabe1, Tomoichiro Oka2, Hirotaka Takagi3

  • 1Division of Laboratory Science, Niigata University Graduate School of Health Sciences, Niigata, Japan.

Nature Communications
|March 31, 2023
PubMed

Insights

Human parechovirus (PeV-A) uses the myeloid-associated differentiation marker (MYADM) to enter cells. MYADM is crucial for PeV-A infection, including the severe PeV-A3 genotype, impacting infant health.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Human parechovirus (PeV-A) is a Picornaviridae family RNA virus with 19 genotypes.
  • While typically causing mild illness, PeV-A3 can lead to severe disease, neurological issues, and death in neonates and infants.

Purpose of the Study:

  • To identify host factors essential for PeV-A entry into human cells.
  • To investigate the role of MYADM in PeV-A infection, particularly PeV-A3.

Main Methods:

  • Gene knockout experiments to assess MYADM's role in PeV-A infection.
  • Transfection of hamster BHK-21 cells with human MYADM to evaluate susceptibility to PeV-A.
  • Analysis of VP0 capsid protein interaction with MYADM.

Main Results:

  • MYADM was identified as a critical host factor for the entry of six PeV-A genotypes (PeV-A1 to PeV-A6), including PeV-A3.
  • Knocking out MYADM expression abolished PeV-A infection in human cells.
  • Expression of human MYADM in resistant BHK-21 cells enabled PeV-A infection and viral production.
  • The VP0 capsid protein of PeV-A3 was shown to interact with an extracellular domain of MYADM.

Conclusions:

  • MYADM is an essential host factor for PeV-A entry.
  • Understanding MYADM's role advances knowledge of PeV-A pathogenesis, especially severe infant cases.
  • MYADM represents a potential target for therapeutic interventions against PeV-A infections.

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