Molecular characterization of a new SARS-CoV-2 recombinant cluster XAG identified in Brazil

Abstract

Recombination events have been described in the Coronaviridae family. Since the beginning of the SARS-CoV-2 pandemic, a variable degree of selection pressure has acted upon the virus, generating new strains with increased fitness in terms of viral transmission and antibody scape. Most of the SC2 variants of concern (VOC) detected so far carry a combination of key amino acid changes and indels. Recombination may also reshuffle existing genetic profiles of distinct strains, potentially giving origin to recombinant strains with altered phenotypes. However, co-infection and recombination events are challenging to detect and require in-depth curation of assembled genomes and sequencing reds. Here, we present the molecular characterization of a new SARS-CoV-2 recombinant between BA.1.1 and BA.2.23 Omicron lineages identified in Brazil. We characterized four mutations that had not been previously described in any of the recombinants already identified worldwide and described the likely breaking points. Moreover, through phylogenetic analysis, we showed that the newly named XAG lineage groups in a highly supported monophyletic clade confirmed its common evolutionary history from parental Omicron lineages and other recombinants already described. These observations were only possible thanks to the joint effort of bioinformatics tools auxiliary in genomic surveillance and the manual curation of experienced personnel, demonstrating the importance of genetic, and bioinformatic knowledge in genomics.

Enhanced recombination among Omicron subvariants of SARS‐CoV‐2 contributes to viral immune escape

“…This was circumvented by subsampling recombinant parent sequences based on the CoV‐lineages database (https://cov-lineages.org/lineage_list.html) and corroborating with their cocirculation data. Moreover, the breakpoint regions we report are largely in coherence with previously published studies 4,5,13–15 …”

“…Some studies have reviewed these CoV‐Lineage entries 11,12 . However, the existence of only a few of these lineages (XA, XB, XC, XD, XE, XF, and XAG) was later validated 4,5,13–15 . To understand the prevalence and significance of SARS‐CoV‐2 recombination lineages, we conducted a comprehensive analysis of publicly available SARS‐CoV‐2 whole genome datasets from November 2019 to July 2022.…”

“…11,12 However, the existence of only a few of these lineages (XA, XB, XC, XD, XE, XF, and XAG) was later validated. 4,5,[13][14][15] To understand the prevalence and significance of SARS-CoV-2 recombination lineages, we conducted a comprehensive analysis of publicly available SARS-CoV-2 whole genome datasets from November 2019 to July 2022. We observed a striking escalation in the appearance of recombinant lineage during the Omicron wave.…”

The Omicron Lineages BA.1 and BA.2 (Betacoronavirus SARS-CoV-2) Have Repeatedly Entered Brazil through a Single Dispersal Hub

“…While we have not found in this work any unreported new mutations in significant frequencies, it is important to note that the Omicron sublineage BA.1.14.1 probably originated in Brazil as a reflection of the expansion of the Omicron variant at the turn of 2021 to 2022. Even more alarming is the emergence of the lineage XAG in Brazil [49], a recombinant of BA.1 and BA.2 that has spread at least to Chile, the United States of America, Denmark, Germany, and Israel. Recombinant lineages may combine the advantageous mutations of the parental lineages, posing a risk of generating highly infectious variants [28,50,51].…”

The SARS-CoV-2 Delta (B.1.617.2) variant with spike N501Y mutation in the shadow of Omicron emergence

“…These data suggest that the prevalence of recombinant forms of SARS-CoV-2 may be consequently low ( Nie et al, 2020 ; Wang et al, 2020 ; VanInsberghe et al, 2021 ). On the other hand, current tracking of SARS-CoV-2 mutations has provided evidence of the contribution of both inter- and intra-variant recombination of SARS-CoV-2 genomes developing emerged recombinants such as XD (Delta AY.4/Omicron BA.1) XE (Omicron BA.1/BA.2), XF (Delta/Omicron BA.1), XL (Omicron BA.1/BA.2), XG (Omicron BA.1/BA.2), XN (Omicron BA.1/BA.2), XQ (Omicron BA.1/BA.2), XR (Omicron BA.1/BA.2), and XAG (Omicron BA.1/BA.2) ( Wang et al, 2022 ; Chakraborty et al, 2022 ; Silva et al, 2022 ). If we observe the target N501Y substitution of SARS-CoV-2 isolated from the patients described in our study and the possibility of co-infection with the 501N variant, both forms of the virus genome would be differentiated already with VirSNiP N501Y/melting curve analysis.…”