A viral phospholipase A2 is required for parvovirus infectivity.
Sequence analysis revealed phospholipase A2 (PLA2) motifs in capsid proteins of parvoviruses. Although PLA2 activity is not known to exist in viruses, putative PLA2s from divergent parvoviruses, human B19, porcine parvovirus, and insect GmDNV (densovirus from Galleria mellonella), can emulate catalytic properties of secreted PLA2. Mutations of critical amino acids strongly reduce both PLA2 activity and, proportionally, viral infectivity, but cell surface attachment, entry, and endocytosis by PLA2-deficient virions are not affected. PLA2 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 PLA2 inhibitors as a new class of antiviral drugs against parvovirus infections and associated diseases.
Zádori
Z
Z
Centre de microbiologie et biotechnologie, INRS-Institut Armand-Frappier Université du Quebec, Laval, Canada.
Szelei
J
J
Lacoste
M C
MC
Li
Y
Y
Gariépy
S
S
Raymond
P
P
Allaire
M
M
Nabi
I R
IR
Tijssen
P
P
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002213:Capsid / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002855:Chromatography, Thin Layer; D004247:DNA / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005822:Genetic Vectors; D017403:In Situ Hybridization; D008247:Lysosomes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D017992:Parvovirus / Q000201:enzymology* / Q000502:physiology*; D010741:Phospholipases A / Q000378:metabolism* / Q000502:physiology*; D054467:Phospholipases A2; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000378:metabolism; D014162:Transfection
D013879:Thioredoxins; D004247:DNA; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium