A viral phospholipase A2 is required for parvovirus infectivity

Sequence analysis revealed phospholipase A(2) (PLA(2)) motifs in capsid proteins of parvoviruses. Although PLA2 activity is not known to exist in viruses, putative PLA(2)s from divergent parvoviruses, human B19, porcine parvovirus, and insect GmDNV (densovirus from Galleria mellonella), can emulate catalytic properties of secreted PLA(2-) Mutations of critical amino acids strongly reduce both PLA(2) activity and, proportionally, viral infectivity, but cell surface attachment, entry, and endocytosis by PLA(2)-deficient virions are not affected. PLA(2) activity is critical for efficient transfer of the viral genome from late endosomes/lysosomes to the nucleus to initiate replication. These findings offer the prospect of developing PLA(2) inhibitors as a new class of antiviral drugs against parvovirus infections and associated diseases.