MODE OF INTERACTION BETWEEN PSEUDORABIES VIRUS AND HEPARAN-SULFATE HEPARIN

It has been demonstrated that the efficient attachment of pseudorabies virus (PrV) is mediated by an interaction between glycoprotein C (gC) and a cellular heparin-like substance (T. C. Mettenleiter, L. Zsak, F . Zuckermann, N. Sugg, H. Kern, and T. Ben-Porat, J. Virol. 64, 278-28 6, 1990). According to the prevalent concept, this interaction is like ly to occur between clusters of basic residues of PrV gC and the negat ively charged sulfate esters and carboxylate groups of heparan sulfate /heparin. To elucidate which of the three major types of sulfate group s of heparan sulfate/heparin are involved in the interaction with PrV, we used selectively N-, 2-O-, and 6-O-desulfated samples and other mo dified heparins as competitors in virus-attachment assays. PrV exhibit ed limited preference for the specific sulfate groups of heparan sulfa te/heparin in accordance with a hierarchy of 6-O- > 2-O- > N-sulfates. In addition, since selective removal of any of the specific sulfates had only a slight effect on the competition capacity of heparin, it is likely that the combination of any two of three types of sulfate grou ps could contribute to an interaction with PrV with an efficiency near ly equal to native, fully sulfated heparin. When tested on different c ell lines the pattern of PrV requirement for the specific O-sulfate gr oups, i.e., 6-O-sulfates > 2-O-sulfates, remained the same. However, d ifferent minimum lengths of heparin fragments were required to inhibit PrV attachment to different cell lines, suggesting a relative virus f lexibility in accommodation to different forms of heparan sulfate. (C) 1996 Academic Press, Inc.