Group V and X secretory phospholipase A2 prevents adenoviral infection in mammalian cells.
sPLA2 (secretory phospholipase A2) enzymes have been implicated in various biological events, yet their precise physiological functions remain largely unresolved. In the present study we show that group V and X sPLA2s, which are two potent plasma membrane-acting sPLA2s, are capable of preventing host cells from being infected with an adenovirus. Bronchial epithelial cells and lung fibroblasts pre-expressing group V and X sPLA2s showed marked resistance to adenovirus-mediated gene delivery in a manner dependent on their catalytic activity. Although adenovirus particles were insensitive to recombinant group V and X sPLA2s, direct addition of these enzymes to 293A cells suppressed both number and size of adenovirus plaque formation. Group V and X sPLA2s retarded the entry of adenovirus into endosomes. Moreover, adenoviral infection was suppressed by LPC (lysophosphatidylcholine), a membrane-hydrolytic product of these sPLA2s. Thus hydrolysis of the plasma membrane by these sPLA2s may eventually lead to the protection of host cells from adenovirus entry. Given that group V and X sPLA2s are expressed in human airway epithelium and macrophages and that the expression of endogenous group V sPLA2 is upregulated by virus-related stimuli in these cells, our present results raise the possibility that group V and X sPLA2s may play a role in innate immunity against adenoviral infection in the respiratory tract.
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
D000256:Adenoviridae / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology* / Q000821:virology*; D005347:Fibroblasts / Q000201:enzymology / Q000821:virology; D015971:Gene Expression Regulation, Enzymologic; D054505:Group V Phospholipases A2; D054509:Group X Phospholipases A2; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D012333:RNA, Messenger / Q000378:metabolism
D008244:Lysophosphatidylcholines; D012333:RNA, Messenger; D010741:Phospholipases A; D054505:Group V Phospholipases A2; D054509:Group X Phospholipases A2; C516365:PLA2G10 protein, human; C516299:PLA2G5 protein, human; D054467:Phospholipases A2; C516366:Pla2g10 protein, mouse; C516300:Pla2g5 protein, mouse