title: Sialic acid on herpes simplex virus type 1 envelope glycoproteins is required for efficient infection of cells.
abstract: Herpes simplex virus type 1 (HSV-1) envelope proteins are posttranslationally modified by the addition of sialic acids to the termini of the glycan side chains. Although gC, gD, and gH are sialylated, it is not known whether sialic acids on these envelope proteins are functionally important. Digestion of sucrose gradient purified virions for 4 h with neuraminidases that remove both alpha2,3 and alpha2,6 linked sialic acids reduced titers by 1,000-fold. Digestion with a alpha2,3-specific neuraminidase had no effect, suggesting that alpha2,6-linked sialic acids are required for infection. Lectins specific for either alpha2,3 or alpha2,6 linkages blocked attachment and infection to the same extent. In addition, the mobility of gH, gB, and gD in sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels was altered by digestion with either alpha2,3 specific neuraminidase or nonspecific neuraminidases, indicating the presence of both linkages on these proteins. The infectivity of a gC-1-null virus, DeltagC2-3, was reduced to the same extent as wild-type virus after neuraminidase digestion, and attachment was not altered. Neuraminidase digestion of virions resulted in reduced VP16 translocation to the nucleus, suggesting that the block occurred between attachment and entry. These results show for the first time that sialic acids on HSV-1 virions play an important role in infection and suggest that targeting virion sialic acids may be a valid antiviral drug development strategy.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, School of Medicine and Public Health, 6630 Medical Sciences Center, 1300 University Avenue, Madison, WI 53706, USA.
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Teuton
authors.forename: Curtis R
authors.initials: CR
authors.lastname: Brandt
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology; D002467:Cell Nucleus / Q000737:chemistry; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D006023:Glycoproteins / Q000378:metabolism / Q000502:physiology*; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000502:physiology*; D037102:Lectins / Q000378:metabolism / Q000494:pharmacology; D019158:N-Acetylneuraminic Acid / Q000378:metabolism / Q000502:physiology*; D009439:Neuraminidase / Q000378:metabolism; D021381:Protein Transport; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014764:Viral Proteins; D053585:Virus Attachment / Q000187:drug effects; D053586:Virus Internalization
chemical_list: D000998:Antiviral Agents; D006023:Glycoproteins; D017405:Herpes Simplex Virus Protein Vmw65; D037102:Lectins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C046998:bovine herpesvirus type-1 glycoproteins; C039447:glycoprotein D, Human herpesvirus 1; C044200:glycoprotein H, herpes simplex virus type 1; C038535:glycoprotein gC, herpes simplex virus type 1; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid