The N-terminal 5-68 amino acids domain of the minor capsid protein VP1 of human parvovirus B19 enters human erythroid progenitors and inhibits B19 infection.

Parvovirus B19 (B19V) infection causes diseases in humans ranging from the mild to severe hematological disorders. The unique region of the minor structural protein VP1 (VP1u) of 227 amino acids harbors strong neutralizing epitopes which elicit dominant immune responses in patients. Recent studies have shown that the VP1u selectively binds to and enters B19V permissive cells through an unknown cellular proteinaceous receptor. In the present study, we demonstrated that purified recombinant VP1u effectively inhibits B19V infection of expanded primary human erythroid progenitors. Furthermore, we identified the amino acid sequence 5-68 of the VP1 (VP1u) is sufficient to confer the inhibition of B19V infection at a level similar to that of the full-length VP1u. structure prediction suggests that the VP1u contains three α-helices. Importantly, we found that the inhibition capability of the minimal domain VP1u is independent of its dimerization but is likely dependent on the structure of the three predicated α-helices. As VP1u outcompetes the full-length VP1u in entering cells, we believe that VP1u functions as a receptor-binding ligand during virus entry. Finally, we determined the effective inhibition potency of VP1u in B19V infection of human erythroid progenitors, which has a half maximal effective concentration (EC) of 67 nM, suggesting an anti-viral peptide candidate to combat B19V infection.Human parvovirus B19 infection causes severe hematological disorders, including transient aplastic crisis, pure red cell aplasia, and hydrops fetalis. A productive B19 infection is highly restricted to human erythroid progenitors in human bone marrow and fetal liver. In the current study, we identified that the N-terminal 5-68 amino acids domain of the minor viral capsid protein VP1 enters expanded human erythroid progenitors, which is nearly 5 times more efficient than the full-length VP1 unique region (1-227aa). Importantly, purified recombinant 5-68aa of the VP1 has a high efficiency in inhibition of parvovirus B19 infection of human erythroid progenitors, which has a half maximal effective concentration (EC) of 67 nM and a low cytotoxicity. The N-terminal 5-68 amino acids holds the potential as an effective antiviral of parvovirus B19 caused hematological disorders, as well as a carrier to deliver proteins to human erythroid progenitors.