NDLI: Secreted phospholipases A2, a new class of HIV inhibitors that block virus entry into host cells

Content Provider	PubMed Central
Author	David, Fenard Lambeau, Gérard Valentin, Emmanuel Lefebvre, Jean-claude Michel, Lazdunski Doglio, Alain
Copyright Year	1999
Abstract	Mammalian and venom secreted phospholipases A2 (sPLA2s) have been associated with a variety of biological effects. Here we show that several sPLA2s protect human primary blood leukocytes from the replication of various macrophage and T cell–tropic HIV-1 strains. Inhibition by sPLA2s results neither from a virucidal effect nor from a cytotoxic effect on host cells, but it involves a more specific mechanism. sPLA2s have no effect on virus binding to cells nor on syncytia formation, but they prevent the intracellular release of the viral capsid protein, suggesting that sPLA2s block viral entry into cells before virion uncoating and independently of the coreceptor usage. Various inhibitors and catalytic products of sPLA2 have no effect on HIV-1 infection, suggesting that sPLA2 catalytic activity is not involved in the antiviral effect. Instead, the antiviral activity appears to involve a specific interaction of sPLA2s to host cells. Indeed, of 11 sPLA2s from venom and mammalian tissues assayed, 4 venom sPLA2s were found to be very potent HIV-1 inhibitors (ID50 < 1 nM) and also to bind specifically to host cells with high affinities (K0.5 < 1 nM). Although mammalian pancreatic group IB and inflammatory-type group IIA sPLA2s were inactive against HIV-1 replication, our results could be of physiological interest, as novel sPLA2s are being characterized in humans.
Related Links	http://dx.doi.org/10.1172/jci6915
Ending Page	618
Page Count	8
Starting Page	611
File Format	PDF
ISSN	00219738
Journal	Journal of Clinical Investigation
Issue Number	5
Volume Number	104
Language	English
Publisher	American Society for Clinical Investigation
Publisher Date	1999-09-01
Access Restriction	Open
Rights Holder	American Society for Clinical Investigation
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine

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