Open AccessHeparan Sulfate Mediates Infection of High-Neurovirulence Theiler's Viruses
Author(s) -
Honey V. Reddi,
Howard L. Lipton
Publication year - 2002
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.76.16.8400-8407.2002
Subject(s) - biology , heparan sulfate , chinese hamster ovary cell , neuraminidase , virus , sialic acid , virology , permissiveness , viral entry , proteoglycan , sulfation , glycosylation , glycoprotein , glycosaminoglycan , receptor , microbiology and biotechnology , viral replication , biochemistry , extracellular matrix
The mechanisms by which Theiler's murine encephalomyelitis virus (TMEV) binds and enters host cells and the molecules involved are not completely understood. In this study, we demonstrate that the high-neurovirulence TMEV GDVII virus uses the glycosaminoglycan heparan sulfate (HS) as an attachment factor that is required for efficient infection. Studies based on soluble HS-mediated inhibition of attachment and infection, removal of HS with specific enzymes, and blocking with anti-HS antibodies establish that HS mediates GDVII virus entry into mammalian cells. Data from defined proteoglycan-deficient Chinese hamster ovary mutant cells further support the role of HS in GDVII infection and indicate that the extent of sulfation is critical for infection. Neuraminidase treatment of proteoglycan-deficient cells restores permissiveness to GDVII virus, indicating that sialic acid hinders direct access of virus to the protein entry receptor. A model of the potential steps in GDVII virus entry into mammalian cells involving HS is proposed.