A heterologous heparin-binding domain can promote functional attachment of a pseudorabies virus gC mutant to cell surfaces

Abstract

The efficient attachment of pseudorabies virus to cultured cells is dependent on an electrostatic interaction between negatively charged cell surface heparan sulfate and the viral envelope glycoprotein gC. Deletion of the first one-third of gC severely impairs virus attachment, but the mutant virions are still capable of entering cells and establishing an infection via a gC-independent pathway. This region of gC contains three clusters of positively charged amino acids that exactly or nearly conform to proposed consensus motifs for heparinbinding domains (HBDs), and the loss of one or more of these potential HBDs may be responsible for the observed attachment defect. To more directly show the involvement of HBDs in pseudorabies virus attachment to cells, we replaced the first one-third of gC with a single, biochemically defined HBD from apolipoprotein B-100. On the basis of the results of attachment, penetration, and heparin competition assays, the heterologous HBD mediated heparan sulfate-dependent virus attachment, but not to fully wild-type levels. Although the intermediate phenotype is not understood, the apolipoprotein B-100 HBD may represent the smallest defined amino acid sequence that promotes functional herpesvirus attachment to cultured cells.

Differences in the susceptibility of herpes simplex virus types 1 and 2 to modified heparin compounds suggest serotype differences in viral entry

“…Within 60 min, approximately half of the virus that had been inhibited by 6-O-DS heparin became resistant to the inhibitory effect of 6-O-DS heparin and, in parallel, about half of the bound virus had penetrated. These results suggest that the transition from susceptibility to resistance to 6-O-DS heparin occurs immediately before or concomitant with penetration and is consistent with a model of primary binding at 4ЊC followed by secondary binding at 37ЊC, as has been described for several other viruses (9)(10)(11)16). N-DA heparin inhibited viral plaque formation throughout the time course.…”

Cell Fusion Activity of Hepatitis C Virus Envelope Proteins

“…GAGs are unbranched polysaccharides that are ubiquitously present on the cell surface, acquiring a net negative charge through N and O sulfation (36). GAG binding domains in the proteins are positively charged regions containing arginine and lysine (23). Interaction with the GAG molecule increases the population of the virus or the concentrations of the virus ligand in the vicinity of its entry receptor, enhancing the overall efficiency of infection.…”

Estudio comparativo entre cepas del virus de la pseudorrabia aisladas en el país y de referencia mediante pruebas físico-químicas, electroforesis en SDS-PAGE y patrones de restricción del ADN

“…Se realiza mediante la interacción de un complejo de glicoproteína (gp) viral con estructuras de proteoglicanos que poseen cadenas de heparan sulfato de la superficie celular. Existen diferentes proteínas virales que permiten la adsorción y la penetración del virus a la célula -gC, gD- (34,55,177). Es un proceso electrostático que no requiere energía, pero sí la presencia de electrolitos.…”

“…Es un proceso electrostático que no requiere energía, pero sí la presencia de electrolitos. No es afectado por la temperatura (17) pero puede ser bloqueado por heparina exógena (34,55,133).…”