Viruses Previously Identified in Brazil as Belonging to HIV-1 CRF72_BF1 Represent Two Closely Related Circulating Recombinant Forms, One of Which, Designated CRF122_BF1, Is Also Circulating in Spain

Abstract

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Those derived from recombination between subtype B and subsubtype F1, with 18 reported, most of them of South American origin, are among the most diverse. In this study, we identified a HIV-1 BF1 recombinant cluster that is expanding in Spain, transmitted mainly via heterosexual contact, which, analyzed in near full-length genomes in four viruses, exhibited a coincident BF1 mosaic structure, with 12 breakpoints, that fully coincided with that of two viruses (10BR_MG003 and 10BR_MG005) from Brazil, previously classified as CRF72_BF1. The three remaining Brazilian viruses (10BR_MG002, 10BR_MG004, and 10BR_MG008) previously identified as CRF72_BF1 exhibited mosaic structures highly similar, but not identical, to that of the Spanish viruses and to 10BR_MG003 and 10BR_MG005, with discrepant subtypes in two short genome segments, located in pol and gp120env. Based on these results, we propose that the five viruses from Brazil previously identified as CRF72_BF1 actually belong to two closely related CRFs, one comprising 10BR_MG002, 10BR_MG004, and 10BR_MG008, which keep their CRF72_BF1 designation, and the other, designated CRF122_BF1, comprising 10BR_MG003, 10BR_MG005, and the viruses of the identified Spanish cluster. Three other BF1 recombinant genomes, two from Brazil and one from Italy, previously identified as unique recombinant forms, were classified as CRF72_BF1. CRF122_BF1, but not CRF72_BF1, was associated with protease L89M substitution, which was reported to contribute to antiretroviral drug resistance. Phylodynamic analyses estimate the emergence of CRF122_BF1 in Brazil around 1987. Given their close phylogenetic relationship and similar structures, the grouping of CRF72_BF1 and CRF122_BF1 in a CRF family is proposed.

Identification of a HIV-1 circulating BF1 recombinant form (CRF75_BF1) of Brazilian origin that also circulates in Southwestern Europe

“…The Brazilian ancestry of CRF75_BF1 is consistent with the circulation of subtypes B and F1 in the country, which have given rise to at least 12 reported CRF_BF1s that circulate in Brazil and a 13th (CRF47_BF1) circulating in Spain but originated in Brazil ( Hill et al, 2022 ). The estimated year of origin of the CRF75_BF1 clade is congruent with the earlier estimated origin of the Brazilian F1 strain (around 1977) ( Bello et al, 2006 ) and is similar to the emergence dates of most other South American CRF_BFs reported in the literature ( Bello et al, 2010 ; Ristic et al, 2011 ; Reis et al, 2017 ; Bacqué et al, 2021 ; Delgado et al, 2021 ; Cañada-García et al, 2022 ).…”

“…With the identification of CRF75_BF1, a total of 6 CRFs of South American ancestry have been originally identified in Western Europe (5 CRF_BF1 and 1 CRF_BC) ( Fernández-García et al, 2010 ; Simonetti et al, 2014 ; Struck et al, 2015 ; Bacqué et al, 2021 ; Delgado et al, 2021 ; Cañada-García et al, 2022 ). This, together with the propagation of HIV-1 variants of South American origin among the European population ( De Oliveira et al, 2010 ; Collaço Verás et al, 2011 ; Thomson et al, 2012 ; Lai et al, 2014 ; Carvalho et al, 2015 ; Delgado et al, 2015 ; Fabeni et al, 2015 ; Vinken et al, 2019 ), points to a close relationship between the HIV-1 epidemics in both continents.…”

“…Interestingly, in the cited studies in Brazil and eastern Spain, all CRF75_BF1 or related viruses were classified by the authors as F1 subsubtype viruses, a fact that exposes the limitations of the analysis of Pr-RT sequences for the classification of HIV-1 variants in molecular epidemiological studies. With the identification of CRF75_BF1, a total of 6 CRFs of South American ancestry have been originally identified in Western Europe (5 CRF_BF1 and 1 CRF_BC) (Fernández-García et al, 2010;Simonetti et al, 2014;Struck et al, 2015;Bacqué et al, 2021;Delgado et al, 2021;Cañada-García et al, 2022). This, together with the propagation of HIV-1 variants of South American origin among the European population (De Oliveira et al, 2010;Collaço Verás et al, 2011;Thomson et al, 2012;Lai et al, 2014;Carvalho et al, 2015;Delgado et al, 2015;Fabeni et al, 2015;Vinken et al, 2019), points to a close relationship between the HIV-1 epidemics in both continents.…”

“…Among CRFs, those derived from subtypes B and F1 are among the most numerous, of which 19 have been reported in the literature, most of them of South American origin, derived from the F1 strain circulating in Brazil, among which CRF12_BF, widely circulating in Argentina and Uruguay ( Thomson et al, 2000 , 2002 ; Carr et al, 2001 ), is the most prevalent. Five of the CRF_BFs of South American origin have been first identified in Western Europe [CRF47_BF1 ( Fernández-García et al, 2010 ), CRF66_BF1 ( Bacqué et al, 2021 ), CRF89_BF1 ( Delgado et al, 2021 ), and CRF122_BF1 ( Cañada-García et al, 2022 ) in Spain; and CRF42_BF1 in Luxembourg ( Struck et al, 2015 )], which reflects the increasing immigration from South America to some Western European countries. Here we identify a new CRF_BF of Brazilian origin through near full-length genome analyses of viruses collected in Spain and Italy.…”