title: Role of sulfatide in vaccinia virus infection.
abstract: BACKGROUND
  Vaccinia virus (VACV) was used as a surrogate of variola virus (genus Orthopoxvirus), the causative agent of smallpox, to study orthopoxvirus infection. VACV infects cells via attachment and fusion of the viral membrane with the host cell membrane. Glycosphingolipids, expressed in multiple organs, are major components of lipid rafts and have been associated with the infectious route of several pathogens.
  
  
  RESULTS
  We demonstrate that the VACV-WR (VACV Western-Reserve strain) displays no binding to Cer (ceramide) or to Gal-Cer (galactosylceramide), but binds to a natural sulfated derivative of these molecules: the Sulf (sulfatide) 3' sulfogalactosylceramide. The interaction between Sulf and VACV-WR resulted in a time-dependent inhibition of virus infection. Virus cell attachment was the crucial step inhibited by Sulf. Electron microscopy showed that SUVs (small unilamellar vesicles) enriched in Sulf bound to VACV particles. Both the A27 and L5 viral membrane proteins were shown to interact with Sulf, indicating that they could be the major viral ligands for Sulf. Soluble Sulf was successful in preventing mortality, but not morbidity, in a lethal mouse model infection with VACV-WR.
  
  
  CONCLUSIONS
  Together the results suggest that Sulf could play a role as an alternate receptor for VACV-WR and probably other Orthopoxviruses.
authors.affiliation: Laboratoire de Virologie, Institut de Recherche Biomédicale des Armées-Antenne du Centre de Recherches du Service de Santé des Armées, 38702 La Tronche Cedex, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Perino
authors.forename: Chwan Hong
authors.initials: CH
authors.lastname: Foo
authors.forename: Daniele
authors.initials: D
authors.lastname: Spehner
authors.forename: Gary H
authors.initials: GH
authors.lastname: Cohen
authors.forename: Roselyn J
authors.initials: RJ
authors.lastname: Eisenberg
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Crance
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Favier
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002518:Ceramides / Q000378:metabolism; D006224:Cricetinae; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000821:virology; D005699:Galactosylceramides / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D013329:Structure-Activity Relationship; D013433:Sulfoglycosphingolipids / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D014615:Vaccinia / Q000188:drug therapy / Q000517:prevention & control* / Q000821:virology*; D014616:Vaccinia virus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D012901:Variola virus / Q000502:physiology; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D002518:Ceramides; D005699:Galactosylceramides; D008024:Ligands; D008565:Membrane Proteins; D013433:Sulfoglycosphingolipids; D014764:Viral Proteins; C084124:I(3)SO3-galactosylceramide