LAUSR

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. ABSTRACT Parvovirus B19 (B19V) infection causes diseases in humans ranging from the mild erythema infectiosum 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 ex vivo expanded primary human erythroid progenitors. Furthermore, we identified that the amino acid (aa) sequence 5-68 of the VP1 (VP1u5-68aa) is sufficient to confer the inhibition of B19V infection at a level similar to that of the full-length VP1u. In silico structure prediction suggests that the VP1u5-68aa contains three α-helices. Importantly, we found that the inhibition capability of the minimal domain VP1u5-68aa is independent of its dimerization but is likely dependent on the structure of the three predicated α-helices. As VP1u5-68aa outcompetes the full-length VP1u in entering cells, we believe that VP1u5-68aa functions as a receptor-binding ligand during virus entry. Finally, we determined the effective inhibition potency of VP1u5-68aa in B19V infection of human erythroid progenitors, which has a half-maximal effective concentration (EC50) of 67 nM, suggesting an antiviral peptide candidate to combat B19V infection. IMPORTANCE 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 ex vivo expanded human erythroid progenitors, which is nearly 5 times more efficient than the full-length VP1 unique region (1-227 aa). Importantly, purified recombinant 5-68 aa of the VP1 has high efficiency in inhibition of parvovirus B19 infection of human erythroid progenitors, which has an EC50 of 67 nM and 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.