CDC Dispatch - SARS-CoV-2 Delta–Omicron Recombinant Viruses, United States. Image Credit: Design_Cells / Shutterstock

CDC study reveals a hybrid spike of SARS-CoV-2 from a delta/omicron recombination event.

The US Centers for Disease Control and Prevention (CDC) conducted nationwide genome surveillance to identify and characterize the delta omicron recombinant genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A total of nine genomes were identified with a delta omicron spike hybrid protein. The study was published in the journal emerging infectious diseases.

Center for Disease Control and Prevention SARS-CoV-2 Delta-Omicron Recombinant Viruses, United States. Image Credit: Design_Cells / Shutterstock

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The United States CDC initiated the National SARS-CoV-2 strain surveillance program to identify, characterize, and monitor emerging variants of SARS-CoV-2. So far, the program has identified 1.8 million SARS-CoV-2 genomes from the United States and submitted them to public databases.

Coronaviruses frequently undergo genetic recombination, an evolutionary process to generate new viral variants with increased transmissibility and pathogenicity. The process is defined as the exchange of genetic material between two distinct viral variants, resulting in the generation of a new variant with new traits.

During the ongoing coronavirus 2019 (COVID-19) pandemic, recombination events between alpha, delta, delta and omicron variants have been documented. The recombinant delta omicron variant is expected to significantly affect the efficacy of vaccines and therapeutics due to genetic differences between variants and the strong ability of the omicron to immune evasion.

In the current study, the scientists aim to identify and characterize recombinant delta omicron genomes in the United States.

Recombinant delta omicron genomes

The scientists identified a total of nine delta-omicron recombination sequences from the National Genomic Surveillance Dataset of the Centers for Disease Control and Prevention using a rapid method for interfacial recombination detection. The method detects a single breakpoint within a given nucleotide range where there are no discriminatory mutations between delta and omicron-bound blocks.

The results revealed that the recombinant sequences contain signature mutations for both delta and omicron variants, changing from delta-associated mutations to omicron-associated mutations between high-protein amino acids 158 and 339.

Previously, Omicron delta recombination events have been identified in the UK and France. However, evidence has indicated that these recombinant variants may have resulted from laboratory contaminations, sequencing errors, or co-infection.

To rule out these possibilities, the scientists in the current study used various sequencing strategies to examine raw read data from specific recombinant sequences generated by the molecular loop and amplicon-based sequencing strategies. The results revealed that the consensus sequences generated by newly applied confirmatory sequencing strategies are functionally identical to the corresponding original sequences.

Furthermore, the scientists fragmented the recombinant sequences at a specific locus within the predicted recombination site. By aligning the fragmented sequences with the reference sequences for the delta and omicron variants, the scientists noted that the first part belonged to the delta clade and the rest belonged to the omicron clade.

Additional sequence analysis confirmed that the characteristic delta mutations coincide with the characteristic omicron mutations in the recombinant variant. Furthermore, the translated spike protein showed a hybrid sequence containing distinct amino acids from both delta and omicron variants with a breakpoint between the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the spike S1 subunit.

Composition of the candidate recombinant SARS-CoV-2 genomes

Composition of the candidate recombinant SARS-CoV-2 genomes. a) Amino acid profiles of putative recombinant substances in the US and UK. Amino acid substitutions associated with the delta variant are shown in orange while the substituents associated with the omicron variant are shown in purple; Figures correspond to the proportion of classified Omicron or Delta sequences containing this substitution (Supplement, https://wwwnc.cdc.gov/EID/article/28/7/22-0526-App1.pdf). Gray boxes indicate common amino acid substitutions in both Omicron and Delta sequences. White boxes indicate no change for Wuhan-Hu-1 virus, while black boxes indicate uncommon variants in the Delta or Omicron sequences in aggregate. Featured groups are displayed; Sequences from the US appear to have recombination within the spike gene, and samples from two UK cohorts show upstream recombination of the spike gene (representing cluster 1 in the UK https://github.com/cov-lineages/pango-designation/issues/ 445, representing Group 2 in the UK https://github.com/cov-lineages/pango-designation/issues/441). 1.1 (Omicron) deletion associated with the failure of the spike gene target (Δ69-70), the receptor-binding domain, and the domain containing the recombination site were observed. b) Percentage of reads supporting each single nucleotide change and deletion around the recombination site from Illumina datasets (IDT xGen amplicons) generated at the Centers for Disease Control and Prevention. Shown are 2 recombinants (EPI_ISL_8981459, EPI_ISL_8981824), next to a representative genome AY.119.2 (delta) ((EPI_ISL_6811176) and a representative genome BA.1.1 (Omicron) (EPI_ISL_9351600). Each bar shows the proportion of reads containing the given A allele in nucleotides. and C, T and G) at each locus for each sample.Asterisks indicate deletions, and variants are related to Wuhan-Hu-1 virus.

Study the importance

The study identifies and characterizes recombinant delta omicron genomes containing a hybrid spike protein. Despite the presence of the recombinant variants in the United States over a six-week period, the number of resulting cases remains low. The majority of cases have been detected in the mid-Atlantic region of the United States. However, scientists were unable to establish an epidemiological association due to a lack of identifying information for samples containing these recombinant genomes.

Scientists recommend continuous monitoring of the genome for rapid detection and monitoring of new recombinant variants due to the strong impact on the overall health of recombinant variants.[if–>[if–>

2022-05-15 03:06:00

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