Elucidation of Early Evolution of HIV-1 Group M in the Congo Basin Using Computational Methods

Abstract

The Congo Basin region is believed to be the site of the cross-species transmission event that yielded HIV-1 group M (HIV-1M). It is thus likely that the virus has been present and evolving in the region since that cross-species transmission. As HIV-1M was only discovered in the early 1980s, our directly observed record of the epidemic is largely limited to the past four decades. Nevertheless, by exploiting the genetic relatedness of contemporary HIV-1M sequences, phylogenetic methods provide a powerful framework for investigating simultaneously the evolutionary and epidemiologic history of the virus. Such an approach has been taken to find that the currently classified HIV-1 M subtypes and Circulating Recombinant Forms (CRFs) do not give a complete view of HIV-1 diversity. In addition, the currently identified major HIV-1M subtypes were likely genetically predisposed to becoming a major component of the present epidemic, even before the events that resulted in the global epidemic. Further efforts have identified statistically significant hot- and cold-spots of HIV-1M subtypes sequence inheritance in genomic regions of recombinant forms. In this review we provide ours and others recent findings on the emergence and spread of HIV-1M variants in the region, which have provided insights into the early evolution of this virus.

Keywords: Congo Basin; HIV-1 group M (HIV-1M); evolution; phylogenetic; sequences.

Figure 1

Example of how a representative selection of sequences from each subtype and CRF was achieved. First, a maximum likelihood tree from all 12 sequences of this subtype was constructed, and then, a selection of one sequence from each of the up to seven most basal lineages from the root was made as a representative sample of the overall known diversity of this particular subtype. Copyright © Oxford University Press, Evol Med Pub Health 2015(1):254–265 (2015), used under Creative Commons CC-BY license.

Figure 2

Schematic representation of how a recombination-free tree is constructed using RDP4. Copyright © American Society for Microbiology, Journal of Virology 90:2221–2229 (2016), used with permission.

Figure 3

Schematic illustration of highly divergent sequences. In this example, a, f, g and h (in bold) represent new sequences from a subtype, X; the solid circle represents a bootstrap value of >70% while an open circle represents a value of <70%. The arrow shows the basal node of subtype X. In this example, ‘a’ clusters with ‘b’ but with <70% bootstrap support; in addition, they form a subtree which also contains ‘c’, ‘d’, ‘e’ and ‘f’ with a <70% bootstrap support; therefore, ‘a’ represents an example of a divergent sequence likely clustering near the base of subtype X (it is also possible though that it clusters nearer the crown). Since the bootstrap support for the branch containing the subtree with ‘c’, ‘d’, ‘e’ and ‘f’ is >70%, ‘d’ is considered to be embedded within the subtype X clade. ‘g’ is located at the base of this subtype. Sequence ‘h’ is a divergent lineage branching outside of subtype X and is likely the extant descendent of a lineage that diverged prior to the diversification of the subtype X MRCA. Copyright © Oxford University Press, Evol Med Pub Health 2015(1):254–265 (2015), used under Creative Commons CC-BY license.

Figure 4

The permutation test used to determine whether certain nucleotides within recombinant HIV genomes have been inherited from parental viruses from particular subtypes more or less frequently than can be accounted for by chance. The nucleotides derived from different subtypes are indicated by different colours. In this case we are interested in nucleotides derived from the orange subtype. Copyright © Oxford University Press, Virus Evolution 4(1):vey015 (2018), used under Creative Commons CC-BY NC license.