Phylodynamics of HIV-1 circulating recombinant forms 12_BF and 38_BF in Argentina and Uruguay

Abstract

Background: Although HIV-1 CRF12_BF and CRF38_BF are two epidemiologically important recombinant lineages circulating in Argentina and Uruguay, little is known about their population dynamics.

Methods: A total of 120 "CRF12_BF-like" and 20 "CRF38_BF-like" pol recombinant sequences collected in Argentina and Uruguay from 1997 to 2009 were subjected to phylogenetic and Bayesian coalescent-based analyses to estimate evolutionary and demographic parameters.

Results: Phylogenetic analyses revealed that CRF12_BF viruses from Argentina and Uruguay constitute a single epidemic with multiple genetic exchanges among countries; whereas circulation of the CRF38_BF seems to be confined to Uruguay. The mean estimated substitution rate of CRF12_BF at pol gene (2.5 x 10-3 substitutions/site/year) was similar to that previously described for subtype B. According to our estimates, CRF12_BF and CRF38_BF originated at 1983 (1978-1988) and 1986 (1981-1990), respectively. After their emergence, the CRF12_BF and CRF38_BF epidemics seem to have experienced a period of rapid expansion with initial growth rates of around 1.2 year-1 and 0.9 year-1, respectively. Later, the rate of spread of these CRFs_BF seems to have slowed down since the mid-1990s.

Conclusions: Our results suggest that CRF12_BF and CRF38_BF viruses were generated during the 1980s, shortly after the estimated introduction of subtype F1 in South America (~1975-1980). After an initial phase of fast exponential expansion, the rate of spread of both CRFs_BF epidemics seems to have slowed down, thereby following a demographic pattern that resembles those previously reported for the HIV-1 epidemics in Brazil, USA, and Western Europe.

Figure 1

Virus analyses. a) Genomic mosaic structure of CRF12_BF and CRF38_BF viruses. Green, subtype F1; blue subtype B; white, unknown subtype. Numbers above breakpoints refer to nucleotide positions in the HXB2 genome. Vertical dotted lines indicate the pol gene fragment (nucleotides 2266-3705) used in the present study. b) Majority-rule Bayesian consensus tree of the pol gene of HIV-1 CRFs_BF circulating in Argentina (red), Uruguay (blue), and Brazil (black). Posterior probability values are indicated only at key nodes. Brackets indicate the monophyletic clusters formed by each CRF. Boxes indicate the two Uruguayan sub-cluters identified within the CRF12_BF clade. Positions of the full-length characterized CRF12_BF and CRF38_BF reference sequences are marked with asterisks. The tree was rooted on midpoint and horizontal branch lengths are drawn to scale with the bar at the bottom indicating 0.03 nucleotide substitutions per site. Representative bootscanning plots of the pol gene fragment of CRF12_BF (A32879) and CRF38_BF (UY03_3389) reference sequences are depicted on the right. Reference sequences used for these analyses were as follows: subtype B (BZ126, blue), subtype F1 (BZ167, green), subtype C (92BR025, gray) and subtype A1 (U455, red).

Figure 2

Time-scaled Bayesian phylogenies and corresponding Bayesian skyline plots (BSP) for the HIV-1 CRF12_BF (a) and CRF38_BF (b) epidemics. Time-scaled phylogenies and BSP were generated under a relaxed molecular clock model using BEAST. Branch lengths of the trees represent time (see the time scale at the X-axis of each graph). BSP represent estimates of effective number of infections (Y-axis; log₁₀ scale) through time (X-axis; calendar years). Median (solid line) and upper and lower 95% HPD (dashed lines) estimates of the effective number of infections are shown in each graph.