Inhibition of HIV-1 Infection by an Intramolecular Antisense Peptide to T20 in gp160

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Abstract
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‐1mB 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‐1MN, were not. However, TA‐1L inhibited infection by HIV‐1MN, 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.