Title: Persistent circulation of highly divergent HIV-1M lineages in the Congo Basin Region
Authors: Tongo M, Dorfman JR, de Oliveira T, Martin DP.
Journal: Virus Evolution,:doi: 10.1093/ve/vew036.039 (2017)
The evolutionary processes that within a century yielded the nine major HIV-1 group M (HIV-1M) lineages and over 72 circulating recombinant forms (CRFs) remain the most important obstacles to the development of both a cure and an effective vaccine. It is still unknown how global HIV populations will respond over the long-term when confronted with efficiently protective vaccines and drug therapies.
It is entirely possible that divergent HIV variants that are presently circulating in diversity hotspots such as Cameroon and the DRC might be the source of future global multi-drug resistant or vaccine evasion re-emergence events. In an effort to discover and characterise more of these highly divergent lineages, we recently performed in-depth characterisation of HIV-1 diversity in Cameroon.
We found that 10% of gag sequences and 5% of nef sequences were not easily classifiable into any of the known HIV-1M clades. In addition, the full length characterisation of 24 unique recombinant forms (URFs) from Cameroon showed that these divergent sequences contained large tracts of sequence that could not be credibly classified as having been derived from parental viruses in the known subtypes. Furthermore, we have found that many of the sequence fragments occurring within CRF04_cpx, CRF06_cpx, CRF11_cpx, CRF18_cpx, CRF25_cpx, CRF27_cpx and CRF49_cpx are in fact likely derived from divergent unclassified parental lineages that may pre-date the current subtypes, even though they are presently identified as derived from currently defined HIV-1M subtypes.
The highly divergent sequence tracts evident within these various HIV-1M genomes might be the extant descendants of pre-epidemic HIV-1 group M lineages (i.e. they may, in a sense, be evolutionary relics). This suggests that large pools of undiscovered HIV-1M genetic diversity likely exist throughout equatorial West Africa.
We hypothesise that viruses belonging to these lineages may have gone largely undetected because of their low pathogenicity and/or transmissibility: characteristics that would be expected to result in the long-term survival of individuals that they manage to infect. This should therefore be manifested by individuals infected with these viruses displaying substantially higher degree of within-individual diversity than is usually displayed by individuals infected by viruses in the main pandemic lineages.
Citation: Tongo M, Dorfman JR, de Oliveira T, Martin DP. Persistent circulation of highly divergent HIV-1M lineages in the Congo Basin Region Virus Evolution,:doi: 10.1093/ve/vew036.039 (2017).