High Degree of HIV-1 Group M (HIV-1M) Genetic Diversity within Circulating Recombinant Forms: Insight into the Early Events of HIV-1M Evolution

Abstract

The existence of various highly divergent HIV-1 lineages and of recombination-derived sequence tracts of indeterminate origin within established circulating recombinant forms (CRFs) strongly suggests that HIV-1 group M (HIV-1M) diversity is not fully represented under the current classification system. Here we used a fully exploratory screen for recombination on a set of 480 near-full-length genomes representing the full known diversity of HIV-1M. We decomposed recombinant sequences into their constituent parts and then used maximum-likelihood phylogenetic analyses of this mostly recombination-free data set to identify rare divergent sequence lineages that fall outside the major named HIV-1M taxonomic groupings. We found that many of the sequence fragments occurring within CRFs (including 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 predate the current subtypes, even though they are presently identified as derived from currently defined HIV-1M subtypes. Our evidence suggests that some of these CRFs are descended predominantly from what were or are major previously unidentified HIV-1M lineages that were likely epidemiologically relevant during the early stages of the HIV-1M epidemic. The restriction of these divergent lineages to the Congo basin suggests that they were less infectious and/or simply not present at the time and place of the initial migratory wave that triggered the global epidemic. A ll HIV-1 group M (HIV-1M) viruses that infect humans cluster phylogenetically within a clade of SIVcpz sequences sampled in southern Cameroon, leading to the conclusion that it is likely that Cameroon was the site of the cross-species transmission event that gave rise to HIV-1M (1, 2). Consistent with the hypothesis that the Congo basin region was the epicenter of the epidemic, the greatest genetic diversity of HIV-1M in terms of both numbers of subtypes and degree of genetic diversity within subtypes has been observed in this region (3-7). The different subtypes that today account for the vast majority of HIV-1M infections worldwide likely moved out from this region, each to populate different parts of the world, during the 1950s and 1960s (8, 9).The HIV-1M classification system that we presently employ is based largely on the order in which these various pandemic HIV-1M lineages were discovered. Viruses discovered early on tended to be classified as belonging to "pure" subtypes, and there has been an understandable tendency for more recently discovered viruses with inconsistent degrees of similarity across their genomes to these pure subtypes to be classified as "recombinant forms" (10). While some of these recombinant forms have only ever been sampled from a single individual (in which case they are called unique recombinant forms [URFs]), others have been sampled from multiple unlinked individuals and are thus called circulating recombinant forms (CRFs). This classification system has Citati...

Time-scale of minor HIV-1 complex circulating recombinant forms from Central and West Africa

“…Other interesting observation was that while subtype A env segment of CRF11_cpx and CRF13_cpx fall within the subtype A/A1 radiation, the subtype A env segments of CRF09_cpx and CRF45_cpx branched as early divergent lineages basally to the root of subtype A/A1. This observation is consistent with the notion that CRF09_cpx and CRF45_cpx likely originated from viruses that diverged close to (or even before) the time of the HIV-1 subtype A progenitor [16]. Our results also points that some of these early divergent lineages are still circulating in the DRC, once two HIV-1 subtype A-like sequences from that country branched basally to the CRF45_cpx clade.…”

“…Our results also points that some of these early divergent lineages are still circulating in the DRC, once two HIV-1 subtype A-like sequences from that country branched basally to the CRF45_cpx clade. The contributions of these lineages to the genesis of some CRFs indicate that they had epidemiological relevance during the early stages of the HIV-1 group M epidemic [16, 49]. …”

“…It was suggested that the low frequencies of many ancient HIV-1 divergent lineages in the human population was caused by its absence during the initial migratory wave of variants that triggered the global epidemic [16]. Similarly, the overall low prevalence of the CRFs_cpx lineages carrying fragments of those ancient may reflect a later emergence of these variants when compared to more prevalent HIV-1 subtypes and CRFs.…”

“…Alternatively, the current low prevalence of many ancient HIV-1 divergent lineages and CRFs_cpx lineages may reveals a lower transmissibility of those variants when compared with the globally circulating HIV-1 clades [16]. Some evidences, however, also argued against this hypothesis.…”

“…Some of the complex CRFs (including CRF04_cpx [5], CRF06_cpx [6], CRF09_cpx [7], CRF11_cpx [8], CRF13_cpx [9], CRF18_cpx [10], CRF25_cpx [11], CRF27_cpx [12], CRF37_cpx [13], CRF45_cpx [14] and CRF49_cpx [15]) carry fragments of rare subtypes (e.g., subtypes H, J and K) and divergent unclassified (U) lineages likely derived from parental strains that may predate the current subtypes [16]. Some of these complex CRFs are widely dispersed in a given African region and reaching particularly high prevalence (40–50%) in certain countries, such as the CRF06_cpx in Burkina Faso [17] and the CRF11_cpx in the Central African Republic [18].…”