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 gp120 and the variable region of human immunoglobulins, we have suggested that the use of this protein as a vaccine component could strongly influence the host immune system, making it more vulnerable to HIV, and in the long term, accelerate disease progression in asymptomatic HIV patients. Using a chimeric primer consisting of the nucleotide sequence derived from the HIV-1 env gene coding for the second conserved region of gp120, and the highly conserved sequence derived from the human immunoglobulin gene coding for the V(H)III domain, we have identified in sera of AIDS patients HIV-1 field isolates carrying the complete and active Chi recombinational hot spot (GCTGGTGG). We have also demonstrated in vivo recombination between the HIV-1 gene coding for the central portion of the gp120 involving the V3 loop and the bacterial gene coding for the clp protease. These results strongly support and reinforce the previous contention and the serious concern that AIDS vaccine candidates carrying the HIV-1 env gene on viral and bacterial vectors, could result in the generation of new pathogens with unpredictable effects on the immune system.
Prljić
J
J
R&D Division, Diapharm, Guernsey, Channel Island, UK.
Veljković
N
N
Doliana
R
R
Colombatti
A
A
Johnson
E
E
Metlas
R
R
Veljković
V
V
D016915:AIDS Vaccines; D000251:Adenosine Triphosphatases / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D049071:Endopeptidase Clp; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015497:HIV-1; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D011995:Recombination, Genetic; D012697:Serine Endopeptidases / Q000235:genetics
D016915:AIDS Vaccines; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D012697:Serine Endopeptidases; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases