Near full-length HIV type 1M genomic sequences from Cameroon

Abstract

Background: Cameroon is the country in which HIV-1 group M (HIV-1M) likely originated and is today a major hotspot of HIV-1M genetic diversity. It remains unclear, however, whether the highly divergent HIV-1M lineages found in this country arose during the earliest phases of the global HIV-1M epidemic, or whether they arose more recently as a result of recombination events between globally circulating HIV-1M lineages.Methodology: To differentiate between these two possibilities, we performed phylogenetic analyses of the near full genome sequences of nine newly sequenced divergent HIV-1M isolates and 15 previously identified, apparently unique recombinant forms (URFs) from Cameroon.Results: Although two of the new genome sequences were clearly classifiable within subtype G, the remaining seven were highly divergent and phylogenetically branched either outside of, or very near the bases of clades containing the well characterised globally circulating viral lineages that they were most closely related to. Recombination analyses further revealed that these divergent viruses were likely complex URFs. We show, however that substantial portions (>1 Kb) of three of the new genome sequences and 15 of the previously characterised Cameroonian URFs have apparently been derived from divergent parental viruses that branch phylogenetically near the bases of the major HIV-1M clades.Conclusions and implications: Our analyses indicate the presence in Cameroon of contemporary descendants of numerous early-diverging HIV-1M lineages. Further efforts to sample and sequence viruses from such lineages could be crucial both for retracing the earliest evolutionary steps during the emergence of HIV-1M in humans, and accurately reconstructing the ancestral sequences of the major globally circulating HIV-1M lineages.

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

“…As has been shown for a number of Cameroonian URFs (20,22), our phylogenetic analyses also indicate that the parental viruses of many HIV-1M genetic variants found in individuals either in or originating from the Congo basin (indicated by bold italic text in Fig. 1 and in Fig.…”

“…Our study and some others in recent years (13,16,37) indicate that it might be useful to at least consider the establishment of some additional guidelines for the classification of novel complex HIV-1M recombinants and divergent sequences such as those which are continually being discovered in equatorial west Africa (20,22). Specifically, whenever a novel URF or CRF is discovered, it should be recommended that an effort be made to phylogenetically characterize the portions of these genomes that are apparently derived from divergent parental lineages, using a well-defined standard (and preferably Los Alamos HIV database-approved) set of representative reference sequences.…”

“…These included (i) 423 sequences from 76 taxonomically recognized subtypes/CRFs (21) obtained from the Los Alamos National Laboratory (LANL) database, (ii) 12 sequences classified as "U" (May 2014) and also from the LANL database, and (iii) 45 genetically divergent sequences from GenBank (May 2014). The 423 sequences representative of the known subtype and CRF lineages were specifically selected to include the broadest diversity of sequences previously identified as belonging to these subtypes/CRFs (22). In brief, this was achieved by constructing maximum-likelihood (ML) trees from all available nearfull-length sequences for each subtype and CRF using FastTree 2 (23), as implemented in RDP4 (24), and selecting one sequence from each of the up to 20 most basal lineages from the root nodes of these subtype/ CRF clades.…”

HIV-1 Unique Recombinant Forms Identified in Slovenia and Their Characterization by Near Full-Length Genome Sequencing

“…These CRFs were shown to probably originate from Central Africa, where they emerged in the late 1950s to late 1960s [43]. Tongo et al (2015) proposed that parts of genomes of the unique recombinant sequences from Cameroon that clustered outside of all identified subtypes and CRF clades are in fact historical lineages that diverged early in the HIV epidemic but did not reach the magnitude of an epidemic like other subtypes did [46].…”

Development of a Versatile, Near Full Genome Amplification and Sequencing Approach for a Broad Variety of HIV-1 Group M Variants

“…Generally, most primers were designed manually based on sequence alignments and primer criteria as follows. An HIV-1 full genome alignment comprised of 480 reference sequences from all major group M (sub)-subtypes and CRFs [32] was shortened to a representative 40 strain-panel. The latter included four references per eight (sub)-subtypes A1, A2, B, C, D, F1, F2, G, and two CRFs, 01_AE, and 02_AG (Results 3.2 ), which make up to the most dominant (sub-)subtypes/CRFs prevailing the five inhabited continents of the world.…”