Functional dissection of the prototype foamy virus glycoprotein heparan sulfate binding site

The minimal HSBS of the PFV GPC is defined by four central, evolutionarily conserved positively charged residues. Substituting these with negatively charged amino acids abolishes HS-dependent attachment and severely reduces specific infectivity. The minor impact of the peripheral residue mutation K₃₅₆E, combined with the lack of evolutionary conservation among most peripheral positively charged residues in primate FV species, suggests these residues play only a secondary role in HS interaction. Furthermore, the residual infectivity of PCSP mutants in HS-deficient cells confirms that HS is an important attachment factor but not an essential entry receptor. The functional homology between PFV and SFVggo GPCs strongly suggests that this conserved PCSP constitutes a universal HS-binding site across all FV species.