HIV-1 GENETIC DIVERSITY

Background: HIV-1 evolves by rapid mutation and by recombination, both processes actively contributing to its genetic diversity. Most of the multiple genetic subtypes and intersubtype recombinations of HIV-1 th at comprise the global pandemic have not been characterized by full ge nome sequencing. Methods: DNA from primary virus cultures on donor per ipheral blood mononuclear cells was used as template for long polymera se chain reaction amplification, molecular cloning, and automated sequ encing of virtually full-length HIV-1 genomes from subtypes A, C, E, G and A/D recombinant forms. Standard phylogenetic analysis methods wer e employed, and some were modified for the detection and mapping of re combinant breakpoints. Results: Subtypes A, B, C and D are largely, if not entirely, distinguishable throughout the genome and show no clear evidence of intersubtype recombination. In contrast, all available se quences of subtypes E and C are recombinant with subtype A. Full-lengt h sequences of subtypes F, H, I and J are still unavailable. Subtype E and G, and some A/D recombinant HIV, have retained the cytoplasmic do main of gp41 from subtype A. Some recombinants possess the matrix and core of one subtype and the outer envelope of another, resembling pseu dotypes. Certain pairs of subtypes may have recombined more often than others. Conclusion: Recombinant HIV-1 have already established a glob al reservoir and are largely responsible for the rapidly expanding sub type E epidemic in Southeast Asia, Recombination may have played a key role in the evolution of HIV-1 and the geographic intermixing of subt ypes, which is increasing, may foster the emergence of a even greater variety of recombinant strains.