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325 Pervasive Recombination in HIV and Its Implications for Cross-Protective Immunity
M. Worobey*, A. Rambaut, and D. L. Robertson
Univ. of Oxford, UK
Background: Although methods for detecting mosaic strains have successfully identified several inter-subtype recombinant HIV-1 lineages, the question of whether recombination is an important evolutionary process within subtypes remains unanswered. One possibility is that recombination occurs frequently between relatively similar strains but falls below the threshold of detectibility of current methods. Alternatively, the current lack of evidence for intra-subtype HIV-1 recombination may reflect limited opportunity for similar strains to recombine if natural infection acts to prevent superinfection by closely related viruses. An accurate understanding of the role of recombination within HIV-1 subtypes is vital not only for evolutionary studies, but also because the success of future vaccines may depend on such cross-protection against similar strains.
Methods: Phylogenetic analysis of naturally circulating viral strains was used to
investigate (i) whether natural infection protects against superinfection with HIV, and (ii) the extent of recombination in HIV-1. We applied a new phylogenetic approach designed to detect recombination even in cases where it has been so prevalent, or has involved sequences so similar, that obvious mosaic patterns may not be apparent. The informative-sites test compares the pattern of polymorphic sites among nucleotide sequences with that expected under a clonal model of evolution.
Results: Recombination, and hence dual infection, was found to occur regularly
within subtypes of HIV-1 group M (statistically significant evidence in subtypes A, B, C, D, G, and CRF01). Notably, there was also evidence for recombination in HIV-1 group O and HIV-2, and between the progenitors of the group M subtypes.
Conclusions: Such pervasive recombination raises serious concerns about using
single phylogenetic trees to depict HIV genetic diversity and evolutionary history, and implies that the difference between a "subtype" and a "circulating recombinant form" is one of degree rather than kind. More importantly, these results indicate that cross-protective immunity is weak even among closely related wild-type HIV strains. Hence, future vaccines may have to surpass naturally circulating strains in ability to prevent subsequent infection.
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