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 A(2) (sPLA(2)) enzymes identified to date, group V and X sPLA(2)s, which are two potent plasma membrane-acting sPLA(2)s, 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 sPLA(2), which is structurally more similar to bee venom PLA(2) than to other mammalian sPLA(2)s, also has the capacity to inhibit adenovirus infection into host cells. Mass spectrometry (MS) demonstrated that group III sPLA(2) hydrolyzes particular molecular species of PC to generate LPC in human bronchial epithelial cells. Remarkably, in addition to the catalytically active sPLA(2) 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 sPLA(2) depends on its N-terminal domain. Finally, our MS analysis provided additional and novel evidence that group III, V and X sPLA(2)s target distinct phospholipid molecular species in cellular membranes.
Mitsuishi
Michiko
M
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Masuda
Seiko
S
Kudo
Ichiro
I
Murakami
Makoto
M
D000258:Adenovirus Infections, Human / Q000201:enzymology / Q000517:prevention & control* / Q000821:virology; D000260:Adenoviruses, Human / Q000472:pathogenicity; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D054520:Group III Phospholipases A2 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D054505:Group V Phospholipases A2 / Q000502:physiology; D054509:Group X Phospholipases A2 / Q000502:physiology; D006801:Humans; D009154:Mutation; D010743:Phospholipids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization
D010743:Phospholipids; D011994:Recombinant Proteins; D054520:Group III Phospholipases A2; D054505:Group V Phospholipases A2; D054509:Group X Phospholipases A2