Identification of AXL as a co-receptor for human parvovirus B19 infection of human erythroid progenitors.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36630517.
- Also identified by DOI 10.1126/sciadv.ade0869 and PMC identifier 9833669.
- Licence recorded as CC BY-NC.
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Abstract
Parvovirus B19 (B19V) infects human erythroid progenitor cells (EPCs) and causes several hematological disorders and fetal hydrops. Amino acid (aa) 5-68 of minor capsid protein VP1 (VP1u<sup>5-68aa</sup>) is the minimal receptor binding domain for B19V to enter EPCs. Here, we carried out a genome-wide CRISPR-Cas9 guide RNA screen and identified tyrosine protein kinase receptor UFO (AXL) as a proteinaceous receptor for B19V infection of EPCs. <i>AXL</i> gene silencing in ex vivo expanded EPCs remarkably decreased B19V internalization and replication. Additions of the recombinant AXL extracellular domain or a polyclonal antibody against it upon infection efficiently inhibited B19V infection of ex vivo expanded EPCs. Moreover, B19V VP1u interacted with the recombinant AXL extracellular domain in vitro at a relatively high affinity (<i>K</i><sub>D</sub> = 103 nM). Collectively, we provide evidence that AXL is a co-receptor for B19V infection of EPCs.
Medical subject headings
- Erythema Infectiosum
- Parvovirus B19, Human
- Axl Receptor Tyrosine Kinase