Unravelling the complicated evolutionary and dissemination history of HIV-1M subtype A lineages

Abstract

Subtype A is one of the rare HIV-1 group M (HIV-1M) lineages that is both widely distributed throughout the world and persists at high frequencies in the Congo Basin (CB), the site where HIV-1M likely originated. This, together with its high degree of diversity suggests that subtype A is amongst the fittest HIV-1M lineages. Here we use a comprehensive set of published near full-length subtype A sequences and A-derived genome fragments from both circulating and unique recombinant forms (CRFs/URFs) to obtain some insights into how frequently these lineages have independently seeded HIV-1M sub-epidemics in different parts of the world. We do this by inferring when and where the major subtype A lineages and subtype A-derived CRFs originated. Following its origin in the CB during the 1940s, we track the diversification and recombination history of subtype A sequences before and during its dissemination throughout much of the world between the 1950s and 1970s. Collectively, the timings and numbers of detectable subtype A recombination and dissemination events, the present broad global distribution of the sub-epidemics that were seeded by these events, and the high prevalence of subtype A sequences within the regions where these sub-epidemics occurred, suggest that ancestral subtype A viruses (and particularly sub-subtype A1 ancestral viruses) may have been genetically predisposed to become major components of the present epidemic.

Patterns of genomic site inheritance in HIV-1M inter-subtype recombinants delineate the most likely genomic sites of subtype-specific adaptation

“…For Subtype A, only fragments belonging to the best sampled sub-subtype of this lineage, sub-subtype A1 ( Tongo et al. 2018 ), were selected.…”

Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes

“…Estimates of the tMRCA from the relaxed clock model implemented in the LSD program were generally comparable to previous estimates in the literature for the corresponding HIV-1 clades (Hemelaar 2012; Wertheim, Fourment, and Kosakovsky Pond 2012) except for subtype A1, for which we obtained a more recent range of estimates (1964–70). For instance, Tongo et al (2018) recently estimated that (sub-)subtype A1 originated around 1946–57 from an analysis of full-length genome sequence data. We note that because our estimate relies on the ‘point estimate’ of the phylogeny reconstructed by maximum likelihood, the confidence intervals reported for our tMRCA estimates underestimate the true level of uncertainty and fixing the tree may skew the mean estimate.…”

Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes

“…Estimates of the times to the most recent common ancestor (tMRCA) from the relaxed clock model implemented in the LSD program were generally comparable to previous estimates in the literature for the corresponding HIV-1 clades [11, 39] except for subtype A1, for which we obtained a more recent range of estimates (1964 to 1970). For instance, Tongo et al [34] recently estimated that (sub-)subtype A1 originated around 1946 - 1957 from an analysis of full-length genome sequence data. We note that because our estimate relies on the ‘point estimate’ of the phylogeny reconstructed by maximum likelihood, the confidence intervals reported for our tMRCA estimates underestimate the true level of uncertainty and fixing the tree may skew the mean estimate.…”