Guanine-rich oligonucleotide modified at the 5' terminal by dimethoxytrityl residue inhibits HIV-1 replication by specific interaction with the envelope glycoprotein.
Previous studies have shown that a guanine-rich oligonucleotide SA-1042, DmTr-TGGGAGGTGGGTCTG, neutralizes HIV-1 infectivity, blocks syncytium formation and inhibits the binding of recombinant gp120 to immobilized soluble CD4 in vitro (Furukawa et al., 1994). We have now investigated the precise mode of action of SA-1042. We show here that SA-1042 specifically antagonizes the binding of anti-V3 loop antibodies or anti-CD4 binding-site antibodies to recombinant gp120, and also blocks the binding of an anti-V3 loop antibody to the V3 peptide (gp120IIIB: aa302-324). In contrast, SA-1042 does not inhibit gp120 binding of monoclonal antibodies directed to other regions of gp120, such as the conserved N-terminal regions (gp120IIIB: aa35-108 or gp120IIIB: aa72-130) or the C-terminal region (gp120IIIB: aa481-496). Furthermore, SA-1042 does not interfere with the binding of monoclonal antibodies directed to other molecules, gp41, CD4, CD11a, CD18, CD26, CD44 or CD54. These data suggest that SA-1042 exerts its antiviral effects by targeting the V3 loop as well as the CD4 binding site on gp120.
Agatsuma
T
T
Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Yamamoto
I
I
Furukawa
H
H
Nishigaki
T
T
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology; D002460:Cell Line; D006147:Guanine; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010446:Peptide Fragments / Q000276:immunology*; D014320:Triphenylmethyl Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D019380:Anti-HIV Agents; D015703:Antigens, CD; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; C107784:SA 1042; D014320:Triphenylmethyl Compounds; D006147:Guanine