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

Biochim Biophys Acta. 2007 Nov;1771(11):1389-96. doi: 10.1016/j.bbalip.2007.09.006. Epub 2007 Oct 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenovirus Infections, Human / enzymology
  • Adenovirus Infections, Human / prevention & control*
  • Adenovirus Infections, Human / virology
  • Adenoviruses, Human / pathogenicity
  • Cell Line
  • Cell Membrane / metabolism
  • Group III Phospholipases A2 / chemistry
  • Group III Phospholipases A2 / genetics
  • Group III Phospholipases A2 / physiology*
  • Group V Phospholipases A2 / physiology
  • Group X Phospholipases A2 / physiology
  • Humans
  • Mutation
  • Phospholipids / metabolism
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Phospholipids
  • Recombinant Proteins
  • Group III Phospholipases A2
  • Group V Phospholipases A2
  • Group X Phospholipases A2