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Journal Article Ppublish 45 citations

PubMed: 39744807 DOI: 10.1002/jmv.70136

Genetic Conservation and Diversity of SARS-CoV-2 Envelope Gene Across Variants of Concern.

J Med Virol 97(1):e70136

Authors: Benjamin M Liu, Qiaobin Yao, Ruth Cruz-Cosme, Casey Yarbrough, Kyah Draper, William Suslovic, Imaan Muhammad, Kaia M Contes, David R Hillyard, Shaolei Teng, Qiyi Tang

Affiliations

  • Division of Pathology and Laboratory Medicine, Children's National Hospital, Washington, District of Columbia, USA.
  • Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
  • Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
  • Department of Microbiology, Immunology and Tropical Medicine, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
  • Children's National Research Institute, Washington, District of Columbia, USA.
  • The District of Columbia Center for AIDS Research, Washington, District of Columbia, USA.
  • Department of Biology, Howard University, Washington, District of Columbia, USA.
  • Department of Microbiology, Howard University College of Medicine, Washington, District of Columbia, USA.
  • Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
  • ARUP Laboratories, Salt Lake City, Utah, USA.

Abstract

SARS-CoV-2 Envelope (E) protein is critical in viral assembly, release, and virulence. E gene was considered highly conserved and evolving slowly. Pan-sarbecoviruses-conserved regions in the E gene have been used as targets for various RT-PCR assays to detect SARS-CoV-2. It remains elusive whether SARS-CoV-2 variants of concern (VOCs) have accumulated significant E mutations that may affect protein stability and diagnostic RT-PCR assays. Herein we aimed to perform a comprehensive genetic analysis on the conservation and diversity of the E gene of SARS-CoV-2 and its VOCs in comparison with other human coronaviruses (HCoVs). In silico analysis of 20 326 HCoV E gene sequences retrieved from GenBank and GISAID suggests that SARS-CoV-2 E gene has multiple pan-HCoVs- and pan-SARS-CoV-2-conserved positions but accumulates significant mutations in VOC B.1.351 and Omicron strains. Mutations were often found in the 5' and 3' variable regions, whereas the central region is conserved. Nucleotide changes C109U and A114G may lead to potential failure of first-line SARS-CoV-2 diagnostic/screening assays. Nucleotide change C212U and its concomitant amino acid substitution Pro71Leu (i.e., C212U/Pro71Leu) is a hallmark mutation of B.1.351 variants, while C26U/Thr9Ile is characteristic of all Omicron variants. Later Omicron subvariants, such as XBB.1.5 and EG.5, additionally acquired the A31G/Thr11Ala mutation, as was confirmed by whole genome sequencing of SARS-CoV-2 in 118 pediatric cases. Wild-type E protein exhibits cytotoxicity to cells, but the mutations Thr9Ile, Thr11Ala, Thr9Ile + Thr11Ala, or Pro71Leu reduces its cytotoxicity. The Thr9Ile + Thr11Ala mutation stabilizes the E proteins of Omicron variants, while Pro71Leu alters the cellular distribution of the E protein, reducing its colocalization with the Golgi body. Altogether, this study not only sheds light on the conservation and diversity of the E gene in SARS-CoV-2 and its VOCs but also informs the improvement and development of SARS-CoV-2 or pan-HCoVs screening and diagnostic assays.

MeSH

Genetic Variation, Genes, Sars-Cov-2, Virology, Severe Acute Respiratory Syndrome-Related Coronavirus, Mutation

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