Human group III phospholipase A2 suppresses adenovirus infection into host cells: Evidence that group III, V and X phospholipase A2s act on distinct cellular phospholipid molecular species

Of 10 mammalian secreted phospholipase A2 (sPLA2) enzymes identified to date, group V and X sPLA2s, which are two potent plasma membrane-acting sPLA2s, are capable of preventing host cells from being infected with adenovirus, and this anti-viral action depends on the conversion of phosphatidylcholine (PC) to lysophosphatidylcholine (LPC) in the host cell membrane. Here, we show that human group III sPLA2, which is structurally more similar to bee venom PLA2 than to other mammalian sPLA2s, also has the capacity to inhibit adenovirus infection into host cells. Mass spectrometry (MS) demonstrated that group III sPLA2 hydrolyzes particular molecular species of PC to generate LPC in human bronchial epithelial cells. Remarkably, in addition to the catalytically active sPLA2 domain, the N-terminal, but not C-terminal, domain unique to this enzyme was required for the anti-adenovirus effect. To our knowledge, this is the first demonstration that the biological action of group III sPLA2 depends on its N-terminal domain. Finally, our MS analysis provided additional and novel evidence that group III, V and X sPLA2s target distinct phospholipid molecular species in cellular membranes.