Tracing the epidemic history of HIV-1 CRF01_AE clusters using near-complete genome sequences

Abstract

Human immunodeficiency virus (HIV) has a number of circulating recombinant forms that are the product of recombination between different HIV subtypes. The first circulating recombinant form of HIV-1 to be identified was CRF01_AE, which originated in Central Africa and is now most prevalent in Southeast and East Asia. In this study, we investigated the timescale, evolutionary history, and population genetics of the HIV-1 CRF01_AE strains primarily responsible for the epidemic in Asia. A further aim of our study was to define and standardize the nomenclature and provide well-characterized reference sequences for the phylogenetic transmission clusters of CRF01_AE. We analysed a data set of 334 near-complete genome sequences from various risk groups, sampled between 1990 and 2011 from nine countries. Phylogenetic analyses of these sequences were performed using maximum likelihood and Bayesian methods. Our study confirms that the diversity of HIV-1 CRF01_AE originated in Central Africa in the mid-1970s, was introduced into Thailand between 1979 and 1982, and began expanding there shortly afterwards (1982-1984). Subsequently, multiple clusters significantly contributed to China's HIV epidemic. A Bayesian skyline plot revealed the rapid expansion of CRF01_AE in China around 1999-2000. We identified at least eight different clusters of HIV-1 CRF01_AE formed by rapid expansion into different risk groups and geographic regions in China since the late 1980s.

Figure 1

Maximum-likelihood phylogeny of HIV-1 CRF01_AE strains. Maximum-likelihood phylogeny of near-complete genome sequences of HIV-1 CRF01_AE. The two circles of colored cells show geographic location (inner circle, A) and risk group (outer circle, B).

Figure. 2

Geographic distribution of HIV-1 CRF01_AE clusters identified in the present study. The geographic distribution of HIV-1 CRF01_AE clusters is shown at the (A) country level, and at the provincial level for (B) China and (C) Vietnam. Each CRF01_AE cluster identified in this study is color-coded, as shown on the left. Maps were obtained from Craft MAP website (http://www.craftmap.box-i.net/).

Figure 3

Regression of the root-to-tip genetic distance against year of sampling for 334 HIV-1 CRF01_AE sequences. Genetic distances are based on the tree in Supplementary Figure S2. Colors indicate different sampling locations.

Figure 4

Bayesian skyline demographic reconstruction of HIV-1 CRF01_AE. The vertical axis shows the effective number of infections (N _e) multiplied by mean viral generation time (τ). The solid line and shaded region represent the median and 95% credibility interval of N _eτ through time.

Figure 5

Maximum-clade-credibility tree estimated from near-complete genome sequences of HIV-1 CRF01_AE. Sequence names include accession number, geographic location, and year of sampling. Only internal nodes with posterior probability support >0.5 are shown with white, grey, and black circles.