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J Biol Chem. 2015 Aug 7;290(32):19833-43. doi: 10.1074/jbc.M114.635508. Epub 2015 Jun 23.

Sialic Acids on Varicella-Zoster Virus Glycoprotein B Are Required for Cell-Cell Fusion.

Author information

1
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.
2
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.
3
From the Department of Immunochemistry, Research Institute for Microbial Diseases and.
4
the Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0017, Japan.
5
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.

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.

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

PMID:
26105052
PMCID:
PMC4528143
DOI:
10.1074/jbc.M114.635508
[Indexed for MEDLINE]
Free PMC Article

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