SINGLE BASIC-AMINO-ACID SUBSTITUTIONS AT POSITION-302 OR POSITION-320IN THE V3 DOMAIN OF HIV TYPE-1 ARE NOT SUFFICIENT TO ALTER THE ANTIVIRAL ACTIVITY OF DEXTRAN SULFATE AND HEPARIN

The third variable domain (V3 domain) of the human immunodeficiency vi rus type 1 (HIV-1) envelope glycoprotein gp120 contains a substantial number of positively charged amino acid residues, We previously demons trated that mutation of basic amino acid residues at position 303, 306 , 309, 313, and 325 in the V3 domain of HIV-1 strain NL4-3 resulted in a dramatic elimination of both virus infectivity and syncytium-induci ng ability, Mutations of arginine at position 302 to serine (R302S) or lysine at position 320 to glutamine (K320Q) had variable effects on i nfectivity for a panel of T cell lines tested, These mutations are loc ated on opposite sides of the Gly-Pro-Gly-Arg-Ala sequence in the cent er of the V3 domain, The R302S and K320Q mutations allowed us to deter mine if these basic residues are important for virus neutralization by polyanionic compounds, Dextran sulfate and heparin inhibited the cyto pathogenicities of both mutants for MT-4 cells, although their 50% ant iviral effective doses were slightly higher than those required to ach ieve complete protection against wild-type HIV-1(NL4-3) replication, T his result emphasizes that the basic amino acids of Arg(302) and Lys(3 20) are not essential for the inhibitory effect of dextran sulfate and heparin on HIV-1 infection.