title: Sialic Acids on Varicella-Zoster Virus Glycoprotein B Are Required for Cell-Cell Fusion.
abstract: Varicella-zoster virus (VZV) is a member of the human Herpesvirus family that causes varicella (chicken pox) and zoster (shingles). VZV latently infects sensory ganglia and is also responsible for encephalomyelitis. Myelin-associated glycoprotein (MAG), a member of the sialic acid (SA)-binding immunoglobulin-like lectin family, is mainly expressed in neural tissues. VZV glycoprotein B (gB) associates with MAG and mediates membrane fusion during VZV entry into host cells. The SA requirements of MAG when associating with its ligands vary depending on the specific ligand, but it is unclear whether the SAs on gB are involved in the association with MAG. In this study, we found that SAs on gB are essential for the association with MAG as well as for membrane fusion during VZV infection. MAG with a point mutation in the SA-binding site did not bind to gB and did not mediate cell-cell fusion or VZV entry. Cell-cell fusion and VZV entry mediated by the gB-MAG interaction were blocked by sialidase treatment. N-glycosylation or O-glycosylation inhibitors also inhibited the fusion and entry mediated by gB-MAG interaction. Furthermore, gB with mutations in N-glycosylation sites, i.e. asparagine residues 557 and 686, did not associate with MAG, and the cell-cell fusion efficiency was low. Fusion between the viral envelope and cellular membrane is essential for host cell entry by herpesviruses. Therefore, these results suggest that SAs on gB play important roles in MAG-mediated VZV infection.
authors.affiliation: From the Department of Immunochemistry, Research Institute for Microbial Diseases and Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan, and tsue@biken.osaka-u.ac.jp.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Suenaga
authors.affiliation: From the Department of Immunochemistry, Research Institute for Microbial Diseases and Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan, and.
authors.forename: Maki
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: From the Department of Immunochemistry, Research Institute for Microbial Diseases and.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Arisawa
authors.affiliation: From the Department of Immunochemistry, Research Institute for Microbial Diseases and Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan, and.
authors.forename: Masako
authors.initials: M
authors.lastname: Kohyama
authors.affiliation: From the Department of Immunochemistry, Research Institute for Microbial Diseases and Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan, and.
authors.forename: Kouyuki
authors.initials: K
authors.lastname: Hirayasu
authors.affiliation: the Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Mori
authors.affiliation: From the Department of Immunochemistry, Research Institute for Microbial Diseases and Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan, and arase@biken.osaka-u.ac.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Arase
mesh_terms: D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006031:Glycosylation; D057809:HEK293 Cells; D014645:Herpesvirus 3, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D008561:Membrane Fusion; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009439:Neuraminidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D017354:Point Mutation; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012794:Sialic Acids / Q000737:chemistry* / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization
chemical_list: C115082:MAG protein, human; D018992:Myelin-Associated Glycoprotein; D011134:Polysaccharides; D011994:Recombinant Proteins; D012794:Sialic Acids; D014759:Viral Envelope Proteins; C090198:glycoprotein B, varicella-zoster virus; D009439:Neuraminidase
keywords: N-linked glycosylation; O-linked glycosylation; herpesvirus; membrane fusion; myelin-associated glycoprotein (MAG); sialic acid; sialic acid-binding immunoglobulin-type lectin 4 (Siglec-4); varicella-zoster virus (VZV); virus entry