title: Herpes simplex virus glycoprotein D acquires mannose 6-phosphate residues and binds to mannose 6-phosphate receptors.
abstract: Herpes simplex viruses (HSV) use multiple and sequential receptors to enter host cells. HSV glycoprotein D (gD) has been implicated in binding to cellular receptors that facilitate virus penetration into cells. We used soluble forms of gD that were expressed in Chinese hamster ovary cells to characterize and identify a putative cellular receptor for HSV as the 275-kDa mannose 6-phosphate/insulin-like growth factor II receptor. Soluble gD also bound to the 46-kDa cation-dependent mannose 6-phosphate (Man-6-P) receptor and was extensively modified with Man-6-P residues on its Asn-linked oligosaccharides. Additionally, soluble gD was a high affinity substrate for N-acetylglucosamine-1-phosphotransferase, the first enzyme in the biosynthetic pathway for the addition of Man-6-P residues to lysosomal enzymes. The membrane form of gD immunoprecipitated from HSV-infected cells also bound to the 275-kDa mannose 6-phosphate/insulin-like growth factor II receptor, albeit poorly, and only a small fraction of the membrane gD was modified with Man-6-P. Notwithstanding this low level of mannose phosphorylation, the interaction between gD and Man-6-P receptors may play a role in some aspect of virus entry or egress.
authors.affiliation: Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: C R
authors.initials: CR
authors.lastname: Brunetti
authors.forename: R L
authors.initials: RL
authors.lastname: Burke
authors.forename: S
authors.initials: S
authors.lastname: Kornfeld
authors.forename: W
authors.initials: W
authors.lastname: Gregory
authors.forename: F R
authors.initials: FR
authors.lastname: Masiarz
authors.forename: K S
authors.initials: KS
authors.lastname: Dingwell
authors.forename: D C
authors.initials: DC
authors.lastname: Johnson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D006801:Humans; D008360:Mannosephosphates / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011485:Protein Binding; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D012995:Solubility; D013329:Structure-Activity Relationship; D014759:Viral Envelope Proteins / Q000378:metabolism*
chemical_list: D008360:Mannosephosphates; D008562:Membrane Glycoproteins; D017527:Receptor, IGF Type 2; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; C027693:mannose-6-phosphate