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 that comprise the global pandemic have not been characterized by full genome sequencing. Methods: DNA from primary virus cultures on donor peripheral blood mononuclear cells was used as template for long polymerase chain reaction amplification, molecular cloning, and automated sequencing of virtually full-length HIV-1 genomes from subtypes A, C, E, G and A/D recombinant forms. Standard phylogenetic analysis methods were employed, and some were modified for the detection and mapping of recombinant 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 sequences of subtypes E and C are recombinant with subtype A. Full-length 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 domain of gp41 from subtype A. Some recombinants possess the matrix and core of one subtype and the outer envelope of another, resembling pseudotypes. Certain pairs of subtypes may have recombined more often than others. Conclusion: Recombinant HIV-1 have already established a global reservoir and are largely responsible for the rapidly expanding subtype E epidemic in Southeast Asia, Recombination may have played a key role in the evolution of HIV-1 and the geographic intermixing of subtypes, which is increasing, may foster the emergence of a even greater variety of recombinant strains.