Testing the Hypothesis of a Recombinant Origin of Human Immunodeficiency Virus Type 1 Subtype E

Abstract

The human immunodeficiency virus type 1 (HIV-1) epidemic in Southeast Asia has been largely due to the emergence of clade E (HIV-1E). It has been suggested that HIV-1E is derived from a recombinant lineage of subtype A (HIV-1A) and subtype E, with multiple breakpoints along the E genome. We obtained complete genome sequences of clade E viruses from Thailand (93TH057 and 93TH065) and from the Central African Republic (90CF11697 and 90CF4071), increasing the total number of HIV-1E complete genome sequences available to seven. Phylogenetic analysis of complete genomes showed that subtypes A and E are themselves monophyletic, although together they also form a larger monophyletic group. The apparent phylogenetic incongruence at different regions of the genome that was previously taken as evidence of recombination is shown to be not statistically significant. Furthermore, simulations indicate that bootscanning and pairwise distance results, previously used as evidence for recombination, can be misleading, particularly when there are differences in substitution or evolutionary rates across the genomes of different subtypes. Taken jointly, our analyses suggest that there is inadequate support for the hypothesis that subtype E variants are derived from a recombinant lineage. In contrast, many other HIV strains claimed to have a recombinant origin, including viruses for which only a single parental strain was employed for analysis, do indeed satisfy the statistical criteria we propose. Thus, while intersubtype recombinant HIV strains are indeed circulating, the criteria for assigning a recombinant origin to viral structures should include statistical testing of alternative hypotheses to avoid inappropriate assignments that would obscure the true evolutionary properties of these viruses.

Worldwide molecular epidemiology of HIV

“…Thus, the "E" designation will be retained for the viruses CRF01_AE. 2,117 CRF01_AE viruses have been documented at low frequencies in several Central African countries, like Central African Republic, Cameroon and the Democratic Republic of Congo.…”

“…This virus emerged among several African countries and became epidemic in the African continent, predominantly in West and West Central Africa, where it represents between 50 to 70% of the circulating strains. 2,24,38,83,91,109,143 Thus, from Africa CRF02_AG they were introduced in Europe and its epidemic has lately been rapidly spreading in France, 137 Belgium, 126 Italy, 90 and United Kingdom. 134 African and European immigrants are responsible by a large panel of CRFs in United Kingdom, such as CRF01_AE, CRF14_BG, CRF03_AB, CRF05_DF, CRF06_cpx, and CRF11_cpx, together with CRF02_AG and several URFs.…”

“…134 African and European immigrants are responsible by a large panel of CRFs in United Kingdom, such as CRF01_AE, CRF14_BG, CRF03_AB, CRF05_DF, CRF06_cpx, and CRF11_cpx, together with CRF02_AG and several URFs. 2,43,82,143 In China where circulates an Indian subtype C in addition to a Chinese subtype B variant (B Ch ), mainly among IDUs, the recombination of both viruses generated two new B/C recombinants, CRF07_BC and CRF08_BC. The CRF07_BC appears to contain two small subtype C segments interspersed with subtype B (a C/B/C configuration).…”

Distinct Human Immunodeficiency Virus Type 1 Subtype A Virus Circulating in West Africa: Sub-Subtype A3

“…In their recommendations, they mapped out criteria for defining sub-subtypes by genetic distance estimates. Within each of the subtypes and sub-subtypes identified, a range of genetic diversity has been noted (1,11,13,18,30). Subtypes are genetically equidistant from one another, with the intersubtype nucleotide distances ranging from 15 to 22% in the gag gene and from 20 to 30% in the env gene (7,11,12,26).…”

Open reading frame structure analysis as a novel genotyping tool for hepatitis E virus and the subsequent discovery of an inter-genotype recombinant

“…The putative breakpoints are located in the hyper-variable region in ORF1. Recombination can be disguised by high mutational rate regions (Anderson et al, 2000), and vice versa. The long branch-lengths of the middle region in Fig.…”