Identification of AXL as a co-receptor for human parvovirus B19 infection of human erythroid progenitors

Area of Science:

• Virology
• Cell Biology
• Hematology

Background:

• Parvovirus B19 (B19V) infects human erythroid progenitor cells (EPCs), leading to hematological disorders and fetal hydrops.
• The minimal receptor binding domain for B19V entry into EPCs is amino acids 5-68 of the VP1 capsid protein (VP1u^5-68aa).

Purpose of the Study:

• To identify the proteinaceous receptor mediating Parvovirus B19 entry into human erythroid progenitor cells.
• To elucidate the role of the identified receptor in B19V infection and replication.

Main Methods:

• Genome-wide CRISPR-Cas9 guide RNA screening was employed to identify host factors involved in B19V infection.
• AXL gene silencing, addition of recombinant AXL extracellular domain, and anti-AXL antibodies were used to assess AXL's role.
• In vitro binding assays (Surface Plasmon Resonance) were performed to quantify the interaction between B19V VP1u and AXL.

Main Results:

• Tyrosine protein kinase receptor UFO (AXL) was identified as a proteinaceous receptor for B19V.
• AXL gene silencing significantly reduced B19V internalization and replication in ex vivo expanded EPCs.
• B19V VP1u demonstrated high-affinity interaction (K_D = 103 nM) with the recombinant AXL extracellular domain in vitro.

Conclusions:

• AXL acts as a co-receptor for Parvovirus B19 infection of human erythroid progenitor cells.
• Targeting the AXL receptor may offer a novel therapeutic strategy to inhibit B19V infections.