ROLE OF SIALYLOLIGOSACCHARIDE BINDING IN THEILERS VIRUS PERSISTENCE

Theiler's murine encephalomyelitis viruses (TMEVs) belong to the Picor naviridae family and are divided into two groups, typified by strain G DVII virus and members of the TO (Theiler's original) group. The highl y virulent GDVII group causes acute encephalitis in mice, while the TO group is less virulent and causes a chronic demyelinating disease whi ch is associated with viral persistence in mice. This persistent centr al nervous system infection with demyelination resembles multiple scle rosis (MS) in humans and has thus become an important model for studyi ng MS. It has been shown that some of the determinants associated with viral persistence are located on the capsid proteins of the TO group. Structural comparisons of two persistent strains (BeAn and DA) and a highly virulent strain (GDVII) showed that the most significant struct ural variations between these two groups of viruses are located on the sites that may influence virus binding to cellular receptors. Most an imal viruses attach to specific cellular receptors that, in part, dete rmine host range and tissue tropism. In this study, atomic models of T MEV chimeras were built with the known structures of GDVII, BeAn, and DA viruses. Comparisons among the known GDVII, BeAn, and DA structures as well as the predicted models for the TMEV chimeras suggested that a gap on the capsid surface next to the putative receptor binding site , composed of residues from VP1 and VP2, may be important in determini ng viral persistence by influencing virus attachment to cellular recep tors, such as sialyloligosaccharides. Our results showed that sialylla ctose, the first three sugar molecules of common oligosaccharides on t he surface of mammalian cells, inhibits virus binding to the host cell and infection with the persistent BeAn virus but not the nonpersisten t GDVII and chimera 39 viruses.