Interaction between pseudorabies virus and heparin/heparan sulfate: Pseudorabies virus mutants differ in their interaction with heparin/heparan sulfate when altered for specific glycoprotein C heparin-binding domain

Interaction between pseudorabies virus and heparin/heparan sulfate : Pseudorabies virus mutants differ in their interaction with heparin/heparan sulfate when altered for specific glycoprotein C heparin-binding domain

Cell surface heparan sulfate serves as an initial receptor for a number of herpesviruses including pseudorabies virus (PrV). It has been demonstrated that the heparan sulfate-binding domain of PrV glycoprotein C is composed of three discrete clusters of basic residues corresponding to amino acids 76-RRKPPR-81, 96-HGRKR-100, and 133-RFYRRGRFR-141, respectively, and that these clusters are functionally redundant, i.e. each of them could independently support PrV attachment to cells (Flynn, S. J., and Ryan, P. (1996) J. Virol. 70, 1355-1364). To evaluate the functional significance of each of these clusters we have used PrV mutants in which, owing to specific alterations in glycoprotein C, the heparan sulfate-binding site is dominated by a single specific cluster. These mutants exhibited different patterns of susceptibility to selectively N-, 2-O-, and 6-O-desulfated heparin preparations in virus attachment/infectivity assay. Moreover PrV mutants differed as regard to efficiency of their attachment to and infection of cells pretreated with relatively low amounts of heparan sulfate-degrading enzymes. Furthermore glycoprotein C species, purified from respective mutants, bound heparin oligosaccharide fragments of different minimum size. These differences suggest that specific clusters of basic amino acids of the heparan sulfate-binding domain of glycoprotein C may support PrV binding to different structural features/stretches within the heparan sulfate chain.

Bergström, T (författare)
Spillmann, DorotheUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)dsp11476 (författare)
Svennerholm, B (författare)
Flynn, S J (författare)
Ryan, P (författare)
Uppsala universitetInstitutionen för medicinsk biokemi och mikrobiologi (creator_code:org_t)

Ingår i:Journal of Biological Chemistry: Elsevier BV273:9, s. 5047-50520021-92581083-351X

Av författaren/redakt...: Trybala, E; Bergström, T; Spillmann, Dorot ...; Svennerholm, B; Flynn, S J; Ryan, P

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