Identification of an active Chi recombinational hot spot within the HIV-1 envelope gene: consequences for development of AIDS vaccines

Because of a sequence similarity between the HIV-1 envelope glycoprotein gp 120 and the variable region of human immunoglobulins, we have suggested tha t the use of this protein as a vaccine component could strongly influence t he host immune system, making it more vulnerable to HIV, and in the long te rm, accelerate disease progression in asymptomatic HIV patients. Using a ch imeric primer consisting of the nucleotide sequence derived from the HIV-1 env gene coding for the second conserved region of gp120, and the highly co nserved sequence derived from the human immunoglobulin gene coding for the VHIII domain, we have identified in sera of AIDS patients HIV-I field isola tes carrying the complete and active Chi recombinational hot spot (GCTGGTGG ). We have also demonstrated in vivo recombination between the HIV-I gene c oding for the central portion of the gp120 involving the V3 loop and the ba cterial gene coding for the clp protease. These results strongly support an d reinforce the previous contention and the serious concern that AIDS vacci ne candidates carrying the HIV-1 env gene on viral and bacterial vectors, c ould result in the generation of new pathogens with unpredictable effects o n the immune system. (C) 1999 Elsevier Science Ltd. All rights reserved.