title: Group V and X secretory phospholipase A2 prevents adenoviral infection in mammalian cells.
abstract: 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.
authors.affiliation: Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Mitsuishi
authors.forename: Seiko
authors.initials: S
authors.lastname: Masuda
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kudo
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
mesh_terms: 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
chemical_list: 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