A Human Intestinal Cell Line Suitable for the Propagation of Human Parechovirus Type 1 to 6 with a Clear Cytopathic Effect

Takagi, Hirotaka; Oka, Takahiro; Ami, Yasushi; Suzaki, Yuriko; Saito, Hiroyuki

doi:10.7883/yoken.jjid.2021.534

Cited by 1 publication

(1 citation statement)

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“…2 , 3 ). We used HT29-DKO cells and another intestinal cell line susceptible to parechovirus infection, HuTu80 18 . To measure PeV-A1 infection over a time course, we used PeV-A1 engineered to express nanoluciferase (PeV-A1-nLuc, Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

MYADM binds human parechovirus 1 and is essential for viral entry

Qiao,

Richards,

Kim

et al. 2024

Nat Commun

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Human parechoviruses (PeV-A) are increasingly being recognized as a cause of infection in neonates and young infants, leading to a spectrum of clinical manifestations ranging from mild gastrointestinal and respiratory illnesses to severe sepsis and meningitis. However, the host factors required for parechovirus entry and infection remain poorly characterized. Here, using genome-wide CRISPR/Cas9 loss-of-function screens, we identify myeloid-associated differentiation marker (MYADM) as a host factor essential for the entry of several human parechovirus genotypes including PeV-A1, PeV-A2 and PeV-A3. Genetic knockout of MYADM confers resistance to PeV-A infection in cell lines and in human gastrointestinal epithelial organoids. Using immunoprecipitation, we show that MYADM binds to PeV-A1 particles via its fourth extracellular loop, and we identify critical amino acid residues within the loop that mediate binding and infection. The demonstrated interaction between MYADM and PeV-A1, and its importance specifically for viral entry, suggest that MYADM is a virus receptor. Knockout of MYADM does not reduce PeV-A1 attachment to cells pointing to a role at the post-attachment stage. Our study suggests that MYADM is a multi-genotype receptor for human parechoviruses with potential as an antiviral target to combat disease associated with emerging parechoviruses.

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Section: Resultsmentioning

confidence: 99%