RRC ID 50339
Author Sasaki M, Anindita PD, Ito N, Sugiyama M, Carr M, Fukuhara H, Ose T, Maenaka K, Takada A, Hall WW, Orba Y, Sawa H.
Title The Role of Heparan Sulfate Proteoglycans as an Attachment Factor for Rabies Virus Entry and Infection.
Journal J Infect Dis
Abstract Rabies virus (RABV) is the causative agent of fatal neurological disease. Cellular attachment is the initial and essential step for viral infections. Although extensive studies have demonstrated that RABV uses various target cell molecules to mediate infection, no specific molecule has been identified as an attachment factor for RABV infection. Here we demonstrate that cellular heparan sulfate (HS) supports RABV adhesion and subsequent entry into target cells. Enzymatic removal of HS reduced cellular susceptibility to RABV infection, and heparin, a highly sulfated form of HS, blocked viral adhesion and infection. The direct binding between RABV glycoprotein and heparin was demonstrated, and this interaction was shown to require HS N- and 6-O-sulfation. We also revealed that basic amino acids in the ectodomain of RABV glycoprotein serve as major determinants for the RABV-HS interaction. Collectively, our study highlights a previously undescribed role of HS as an attachment factor for RABV infection.
Volume 217(11)
Pages 1740-1749
Published 2018-5-5
DOI 10.1093/infdis/jiy081
PII 4909726
PMID 29529215
MeSH A549 Cells Cell Line Cell Line, Tumor Glycoproteins / metabolism Heparan Sulfate Proteoglycans / metabolism* Humans Rabies / pathology* Rabies virus / metabolism Rabies virus / pathogenicity* Virus Internalization
IF 5.186
Times Cited 11
Resource
Human and Animal Cells A549(RCB0098) HuH-7(RCB1942) SK-N-SH(RCB0426)