Abstract
Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Among 110 reported in the literature, 17 are BF1 intersubtype recombinant, most of which are of South American origin. Among these, all 5 identified in the Southern Cone and neighboring countries, except Brazil, derive from a common recombinant ancestor related to CRF12_BF, which circulates widely in Argentina, as deduced from coincident breakpoints and clustering in phylogenetic trees. In a HIV-1 molecular epidemiological study in Spain, we identified a phylogenetic cluster of 20 samples from 3 separate regions which were of F1 subsubtype, related to the Brazilian strain, in protease-reverse transcriptase (Pr-RT) and of subtype B in integrase. Remarkably, 14 individuals from this cluster (designated BF9) were Paraguayans and only 4 were native Spaniards. HIV-1 transmission was predominantly heterosexual, except for a subcluster of 6 individuals, 5 of which were men who have sex with men. Ten additional database sequences, from Argentina (n = 4), Spain (n = 3), Paraguay (n = 1), Brazil (n = 1), and Italy (n = 1), branched within the BF9 cluster. To determine whether it represents a new CRF, near full-length genome (NFLG) sequences were obtained for 6 viruses from 3 Spanish regions. Bootscan analyses showed a coincident BF1 recombinant structure, with 5 breakpoints, located in p17gag, integrase, gp120, gp41-rev overlap, and nef, which was identical to that of two BF1 recombinant viruses from Paraguay previously sequenced in NFLGs. Interestingly, none of the breakpoints coincided with those of CRF12_BF. In a maximum likelihood phylogenetic tree, all 8 NFLG sequences grouped in a strongly supported clade segregating from previously identified CRFs and from the CRF12_BF “family” clade. These results allow us to identify a new HIV-1 CRF, designated CRF66_BF. Through a Bayesian coalescent analysis, the most recent common ancestor of CRF66_BF was estimated around 1984 in South America, either in Paraguay or Argentina. Among Pr-RT sequences obtained by us from HIV-1-infected Paraguayans living in Spain, 14 (20.9%) of 67 were of CRF66_BF, suggesting that CRF66_BF may be one of the major HIV-1 genetic forms circulating in Paraguay. CRF66_BF is the first reported non-Brazilian South American HIV-1 CRF_BF unrelated to CRF12_BF.
Highlights
One of the most distinctive features of HIV-1 evolution is its high recombinogenic potential, possibly the greatest among human pathogens, which is reflected in the high frequency of unique recombinant forms (URFs), each generated in a duallyor multiply-infected individual, found wherever different genetic forms circulate in the same population (Nájera et al, 2002)
In a molecular epidemiology study on HIV-1 in Spain we identified a cluster of 20 viruses of F1 subsubtype in protease-reverse transcriptase (Pr-RT), that in integrase, sequenced in 4 samples, were of subtype B, which was designated BF9
14 individuals were from Paraguay [with the remaining 6 being from Spain (n = 4), Argentina, and Equatorial Guinea] and all 3 other database sequences from samples collected in Spain were from Latin Americans, one each from Paraguay, Argentina, and an unspecified country
Summary
One of the most distinctive features of HIV-1 evolution is its high recombinogenic potential, possibly the greatest among human pathogens, which is reflected in the high frequency of unique recombinant forms (URFs), each generated in a duallyor multiply-infected individual, found wherever different genetic forms circulate in the same population (Nájera et al, 2002). 4 CRF_BFs related to CRF12_BF, as evidenced by shared breakpoints and phylogenetic clustering, were identified in the Southern Cone of South America or neighboring countries, CRF17_BF (Aulicino et al, 2012), CRF38_BF (Ruchansky et al, 2009), CRF44_BF (Delgado et al, 2010), and CRF89_BF (Delgado et al, 2021), the last three having clear country associations, with Uruguay, Chile, and Bolivia, and Peru, respectively Due to their common ancestry, these 5 CRFs and related URFs have been proposed to constitute a “family” of recombinant viruses (Thomson and Nájera, 2005; Zhang et al, 2010; Delgado et al, 2021). Unlike all South American CRF_BFs identified to date outside of Brazil, it has no relationship with CRF12_BF
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