Single basic amino acid substitutions at position 302 or 320 in 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 virus type 1 (HIV-1) envelope glycoprotein gp120 contains a substantial number of positively charged amino acid residues. We previously demonstrated 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-inducing ability. Mutations of arginine at position 302 to serine (R302S) or lysine at position 320 to glutamine (K320Q) had variable effects on infectivity for a panel of T cell lines tested. These mutations are located on opposite sides of the Gly-Pro-Gly-Arg-Ala sequence in the center of the V3 domain. The R302S and K320Q mutations allowed us to determine if these basic residues are important for virus neutralization by polyanionic compounds. Dextran sulfate and heparin inhibited the cytopathogenicities of both mutants for MT-4 cells, although their 50% antiviral effective doses were slightly higher than those required to achieve complete protection against wild-type HIV-1NL4-3 replication. This result emphasizes that the basic amino acids of Arg302 and Lys320 are not essential for the inhibitory effect of dextran sulfate and heparin on HIV-1 infection.
Okada
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Department of Cell, Molecular, and Structural Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Gurney
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ME
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology*; D001120:Arginine / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D016264:Dextran Sulfate / Q000494:pharmacology*; D004563:Electrochemistry; D005973:Glutamine / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008239:Lysine / Q000235:genetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D012694:Serine / Q000235:genetics
D000998:Antiviral Agents; D017931:DNA Primers; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D005973:Glutamine; D012694:Serine; D006493:Heparin; D016264:Dextran Sulfate; D001120:Arginine; D008239:Lysine