Simian herpes B virus (SHBV) is the herpes simplex virus (HSV) homologue for the speciesMacaca. Unlike in its natural host, and unlike other animal herpesviruses, SHBV causes high mortality in accidentally infected humans. SHBV-infected cells, like those infected with HSV-1 and equine herpesvirus types 1 and 4, express complement C3 receptor activity. To study immunoregulatory functions involved in susceptibility/resistance against interspecies transmission, the SHBV glycoprotein C (gC SHBV ) gene (encoding 467 aa) was isolated. Sequence analysis revealed amino acid identity with gC proteins from HSV-2 (46?9 %), HSV-1 (44?5 %) and pseudorabies virus (21?2 %). Highly conserved cysteine residues were also noted. Similar to gC HSV-2 , gC SHBV is less glycosylated than gC HSV-1 , resulting in a molecular mass of 65 kDa if expressed in replication-deficient vaccinia virus Ankara. Stable transfectants expressing full-length gC SHBV on the cell surface induced C3 receptor activity and were substantially protected from complement-mediated lysis; no protection was observed with control constructs. This suggests that expression of the gC homologues on infected cell surfaces might also contribute to the survival of infected cells in addition to decreased virion inactivation. Interestingly, soluble gC SHBV isolated from protein-free culture supernatants did not interfere with the binding of the alternative complement pathway activator properdin to C3b, which is similar to our findings with gC HSV-2 and could be attributed to major differences in the amino-terminal portion of the protein with extended deletions in both gC SHBV and gC HSV-2 . Binding of recombinant gC SHBV to polysulphates was observed. This, together with the heparin-sensitivity of the gC SHBV -C3 interaction on the infected cell surface, suggests a role in adherence to heparan sulphate, similar to the gC proteins of other herpesviruses.