SARS-CoV-2 spike protein diversity at an intra-host level, among SARS-CoV-2 infected individuals in South Africa, 2020 to 2022

PLoS One. 2023 May 30;18(5):e0286373. doi: 10.1371/journal.pone.0286373. eCollection 2023.

Abstract

Intra-host diversity studies are used to characterise the mutational heterogeneity of SARS-CoV-2 infections in order to understand the impact of virus-host adaptations. This study investigated the frequency and diversity of the spike (S) protein mutations within SARS-CoV-2 infected South African individuals. The study included SARS-CoV-2 respiratory samples, from individuals of all ages, received at the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic hospital, Gauteng, South Africa, from June 2020 to May 2022. Single nucleotide polymorphism (SNP) assays and whole genome sequencing were performed on a random selection of SARS-CoV-2 positive samples. The allele frequency (AF) was determined using TaqMan Genotyper software for SNP PCR analysis and galaxy.eu for analysis of FASTQ reads from sequencing. The SNP assays identified 5.3% (50/948) of Delta cases with heterogeneity at delY144 (4%; 2/50), E484Q (6%; 3/50), N501Y (2%; 1/50) and P681H (88%; 44/50), however only heterogeneity for E484Q and delY144 were confirmed by sequencing. From sequencing we identified 9% (210/2381) of cases with Beta, Delta, Omicron BA.1, BA.2.15, and BA.4 lineages that had heterogeneity in the S protein. Heterogeneity was primarily identified at positions 19 (1.4%) with T19IR (AF 0.2-0.7), 371 (92.3%) with S371FP (AF 0.1-1.0), and 484 (1.9%) with E484AK (0.2-0.7), E484AQ (AF 0.4-0.5) and E484KQ (AF 0.1-0.4). Mutations at heterozygous amino acid positions 19, 371 and 484 are known antibody escape mutations, however the impact of the combination of multiple substitutions identified at the same position is unknown. Therefore, we hypothesise that intra-host SARS-CoV-2 quasispecies with heterogeneity in the S protein facilitate competitive advantage of variants that can completely/partially evade host's natural and vaccine-induced immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / epidemiology
  • Humans
  • SARS-CoV-2* / genetics
  • South Africa / epidemiology
  • Spike Glycoprotein, Coronavirus / genetics

Substances

  • spike protein, SARS-CoV-2
  • Spike Glycoprotein, Coronavirus

Grants and funding

The National Research Foundation rating funding (RA191126494205) received by Dr. Florette K. Treurnicht and Kathleen Subramoney received a National Health Laboratory Service (NHLS) Research Trust Development Grant (GRANT0004 94811) and a National Research Foundation Thuthuka grant (GRANT95853 93401). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors, and therefore, the NRF do not accept any liability in regard thereto. Research reported in this publication was supported by the South African Medical Research Council (SAMRC) with funds received from the Department of Science and Innovation. The content and findings reported and illustrated here are the sole deduction, view and responsibility of the researcher and do not reflect the official position and sentiments of the SAMRC or the Department of Science and Innovation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.