Multi-branched peptides based on the HIV-1 V3 loop consensus motif inhibit HIV-1 and HIV-2 infection in CD4+ and CD4- cells.

The V3 loop is an hypervariable region of the HIV-1 surface envelope glycoprotein gp120 that is able to generate neutralizing antibodies. These antibodies are generally type-specific. They inhibit the interaction between the V3 loop and the membrane molecules involved in virus-cell and cell-cell fusion. Synthetic peptides based on the V3 loop sequence have been tentatively used to block the fusion process, but the results were unsuccessful. In this report, we confirm that monomeric V3 peptides are devoid of any anti-HIV activity. However, we found that, when assembled in a synthetic polymeric construction (SPC), these peptides have been able to inhibit the infection of human CD4+ lymphocytes and macrophages as well as CD4- epithelial intestinal cells by distantly related isolates of HIV-1 and HIV-2. V3 SPCs, based on the consensus HIV-1 sequence, may therefore represent a new class of therapeutically useful anti-HIV agents able to neutralize a wide range of viral isolates in both CD4+ and CD4- susceptible cells.