Inhibition of HIV-1 infection by an intramolecular antisense peptide to T20 in gp160.
Antisense amino acids are amino acids which can be translated from the corresponding anti-codons of a sense amino acid. Antisense peptides encoded by the noncoding DNA strand have a tendency to interact with each other. We have demonstrated that antisense peptide sequences are present intramolecularly, and these may contribute to the folding and maintenance of the tertiary structure of a protein. T20 is a synthetic peptide with an amino acid sequence in the gp41 of HIV-1 and has been demonstrated to be a potent inhibitor of HIV-1 infection. We searched for intramolecular peptide sequences which are antisense to portions of T20. A synthetic peptide (TA-1L) consisting of amino acids 84 to 97 of gp160, which contains an antisense peptide sequence (TA-1) to T20, was shown to inhibit HIV-1(IIIB) infection of MT-4 cells. Interaction of these antisense peptides could be involved in sustaining HIV-1 infectivity. The TA-1L site, which exists in the C1 domain of gp160, is highly homologous among strains of HIV-1, especially at TA-1 and in the amino acids flanking the C terminus. Although the TA-1 sites of 18 out of 30 HIV-1 strains were antisense to the T20 region, those of the remaining 12 strains, including HIV-1(MN), were not. However, TA-1L inhibited infection by HIV-1(MN), which has no antisense peptide in T20 corresponding to TA-1, although the inhibitory effect was weaker. TA-1L may thus also interfere with the gp160 interaction with CD4, which has an antisense sequence to TA-1.
Imai
M
M
Department of Molecular Biology, Nagoya City University School of Medicine, Aichi, Japan.
Okada
N
N
Okada
H
H
D000595:Amino Acid Sequence; D016375:Antisense Elements (Genetics); D002460:Cell Line; D000077560:Enfuvirtide; D019302:HIV Envelope Protein gp160 / Q000737:chemistry*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D016375:Antisense Elements (Genetics); D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D010455:Peptides; D000077560:Enfuvirtide