title: Salivary lactoferrin is recognized by the human herpesvirus-8.
abstract: Human herpesvirus-8 (HHV-8) is commonly detected in all epidemiologic forms of Kaposi's sarcoma. Despite the broad cellular tropism of HHV-8, studies on mucosal shedding of HHV-8 have shown that infectious particles are restricted to saliva isolated from the oropharynx. We used biotinylated purified HHV-8 particles in a direct binding assay to whole clarified human salivary samples isolated from HHV-8-infected and uninfected individuals. We found that the major binding activity was carried out by a protein of 78-kDa size, which was further characterized as human lactoferrin (hLf) using 2-D electrophoresis and MALDI-ToF analysis. Preliminary comparison of HHV-8 binding activity of 76 salivary samples from HHV-8-infected and uninfected individuals showed that 7.8% of the uninfected population exhibited a form of Lf not recognized by HHV-8. Deglycosylation of hLf by PNGase F did not reduce HHV-8 binding activity, whereas endoproteinase cleavage of native hLf generated a non-glycosylated 8-kDa peptide recognized by HHV-8 particles and was located at the position Ala606-Tyr679 in the native hLf amino acid sequence, corresponding to the C-terminal region of the glycoprotein. This work identify the lactoferrin in saliva as a ligand for HHV-8 and suggests that this glycoprotein could be used as a carrier for the viral particles.
authors.affiliation: Laboratoire de Microbiologie Cutanée, Pavillon Tarnier, Groupe Hospitalier Cochin-Port Royal, Université Paris V, Paris, France. philippe.grange@cch.ap-hop-paris.fr
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Grange
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Caroline
authors.initials: C
authors.lastname: Chauvel
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Escande
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupin
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D006566:Herpesviridae Infections / Q000378:metabolism* / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D007781:Lactoferrin / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008875:Middle Aged; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012463:Saliva / Q000378:metabolism*
chemical_list: D008024:Ligands; D007781:Lactoferrin