Human immunodeficiency virus type 1 (HIV-1) sequences of the major group M are classified into nine subtypes (A-D, F-H, J, and K), six sub-subtypes (A1–A4, and F1–F2), and a variety of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) (Los Alamos HIV sequence database: http://hiv-web.lanl.gov/). The subtype F1 causes a small number of infections globally (<1%) ; but it is particularly prevalent in some specific countries from Europe, South America, and Central Africa, either in its non-recombinant form, or as part of recombinant genomes.
In Europe, non-recombinant subtype F1 strains reach a high prevalence (>70%) among Romanian children and adults [2–5]. This Romanian epidemic was probably caused by the introduction of one subtype F1 virus into the adult population sometime before it appeared in 1989 among institutionalized children . In South America, subtype F1 and mainly BF1 recombinant variants are prevalent (>10%) in countries from the Southern cone (Argentina, Brazil, Chile, Paraguay, and Uruguay), particularly among intravenous drug users and heterosexual populations [7–22]. A previous study suggested that the subtype F1 and BF1 epidemics in South America were initiated by the introduction, through Brazil, of a single founder subtype F1 strain around the middle-late 1970s . Several studies have shown that the South American and Romanian epidemics are the result of distinct subtype F1 introductions [3, 4, 6, 23]; but the geographic epicenter(s) of these subtype F1 epidemics is one of the most puzzling aspects in the worldwide spread of the HIV-1.
The overall prevalence of subtype F1 in Africa is very low, and most of the subtype F1 infections initially described in the continent were from the Democratic Republic of Congo (DRC). Although subtype F1 forms represent a small percentage (<5%) of the HIV-1 strains circulating in the DRC [24–30], sporadic cases of subtype F1 and CRF05_DF infections have been reported in Belgium and the Netherlands among individuals with a direct epidemiological link to the DRC [31–34]; this indicates that this country could be an important epicenter of the world-wide dispersion of both pure and recombinant subtype F1 strains. The most extensive phylogenetic analysis of subtype F1 strains circulating worldwide performed to date, however, revealed that although sequences from the DRC fell in a basal position within the subtype F1 phylogeny, they were only weakly associated with the South American and Romanian clades .
Angola is a Central African country bordered by the DRC, Republic of the Congo, Namibia and Zambia. Like in the DRC, the HIV-1 epidemic in Angola is characterized by the circulation of all group M subtypes and sub-subtypes, a high number of URFs, and several unclassifiable sequences [35–37]. Two recent studies, based on the analysis of partial genome regions, described an unusual high prevalence of subtype F1 infections in Angola, ranging from 8% to 16% [35, 37]. Angola maintains strong social, cultural and economic relationships with Brazil. Noteworthy, the estimated onset date of the subtype F1 epidemic in Brazil (and South America) was around 1975–1980 [23, 38, 39], coinciding with the beginning of the Angolan civil war in 1975 that was followed by a wave of emigration. These observations have lead us to suggest that the subtype F1 found in South America could have been originated from Angola .
To further test this hypothesis, we recovered nine partial and four full-length genome sequences from subtype F1 HIV-1 isolates from Angola and investigated the phylogenetic relationship of these strains with other subtype F1 strains isolated worldwide. We also estimated the onset year of the HIV-1 subtype F1 epidemic in Central Africa based on the analysis of 47 non-contemporary env gene sequences of African origin sampled over a period of 22 years (1984–2006).