Abstract
Although the first HIV circulating recombinant form (CRF01_AE) is the predominant strain in many Asian countries, it is uncommonly found in the Congo Basin from where it first originated. To fill the gap in the evolutionary history of this important strain, we sequenced near complete genomes from HIV samples with subgenomic CRF01_AE regions collected in Cameroon and the Democratic Republic of the Congo from 2001 to 2006. HIV genomes were generated from N = 13 plasma specimens by next-generation sequencing of metagenomic libraries prepared with spiked primers targeting HIV, followed by Sanger gap-filling. Genome sequences were aligned to reference strains, including Asian and African CRF01_AE sequences, and evaluated by phylogenetic and recombinant analysis to identify four CRF01_AE strains from Cameroon. We also identified two CRF02, one CRF27, and six unique recombinant form genomes (01|A1|G, 01|02|F|U, F|G|01, A1|D|01, F|G|01, and A1|G|01). Phylogenetic analysis, including the four new African CRF01_AE genomes, placed these samples as a bridge between basal Central African Republic CRF01_AE strains and all Asian, European, and American CRF01_AE strains. Molecular dating confirmed previous estimates indicating that the most recent common CRF01_AE ancestor emerged in the early 1970s (1968–1970) and spread beyond Africa around 1980 to Asia. The new sequences and analysis presented in this study expand the molecular history of the CRF01_AE clade, and are illustrated in an interactive Next Strain phylogenetic tree, map, and timeline at (https://nextstrain.org/community/EduanWilkinson/hiv-1_crf01).
Highlights
CRF01_AE was the first circulating recombinant form (CRF) to be identified in the HIV type 1 (HIV-1) epidemic.[1,2] The genome structure of this virus appeared to be a mosaic strain containing a mixture of subtype A and portions of sequences that did not cluster with other known subtypes of HIV-1 at the time
A set of N = 13 specimens with subgenomic sequences classified as CRF01 was identified from previous viral diversity studies conducted in Cameroon and DRC for complete genome sequencing
A range of 4.11–5.32 log copies/ml HIV RNA was detected among samples with previous viral load results available (N = 7)
Summary
CRF01_AE was the first circulating recombinant form (CRF) to be identified in the HIV type 1 (HIV-1) epidemic.[1,2] The genome structure of this virus appeared to be a mosaic strain containing a mixture of subtype A and portions of sequences that did not cluster with other known subtypes of HIV-1 at the time. The non-A regions (portions of vif, vpr, env, nef, and 3¢ long terminal repeat) were classified as subtype E, a complete subtype E genome has not been identified to date.
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