The globoside receptor triggers structural changes in the B19 virus capsid that facilitate virus internalization

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Human parvovirus B19 (B19V) utilizes globoside (Gb4Cer), Ku80 autoantigen, and α5β1 integrin as receptors/coreceptors.
• The precise roles and interaction mechanisms of these receptors with B19V remain largely undefined.

Purpose of the Study:

• To elucidate the specific role of Gb4Cer, Ku80, and α5β1 integrin in B19V attachment and internalization.
• To investigate the conformational changes in the B19V capsid upon receptor interaction and their impact on infectivity.

Main Methods:

• Utilized UT7/Epo cells with varying receptor expression levels.
• Employed antibodies against Gb4Cer and VP1u to block viral attachment and internalization.
• Analyzed virus-cell colocalization and infectivity post-receptor detachment.

Main Results:

• Gb4Cer and CD49e (integrin alpha-5) were highly expressed, while Ku80 was insignificant in UT7/Epo cells.
• B19V colocalized with Gb4Cer and, to a lesser extent, CD49e; only anti-Gb4Cer antibodies disrupted attachment.
• Virus detachment from Gb4Cer enhanced subsequent binding and infectivity, linked to VP1 N-terminus (VP1u) exposure.

Conclusions:

• Gb4Cer serves as the primary B19V attachment receptor and orchestrates capsid rearrangements essential for internalization.
• The VP1u region's exposure, mediated by Gb4Cer, is critical for B19V internalization.
• B19V's ability to detach and reattach increases the likelihood of productive infections.