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SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity

Author

Listed:
  • Stella Hartmann

    (University of Chicago
    University of Chicago)

  • Lisa Radochonski

    (University of Chicago
    University of Chicago)

  • Chengjin Ye

    (Texas Biomedical Research Institute)

  • Luis Martinez-Sobrido

    (Texas Biomedical Research Institute)

  • Jueqi Chen

    (University of Chicago
    University of Chicago)

Abstract

SARS-CoV-2 hijacks multiple organelles for virion assembly, of which the mechanisms have not been fully understood. Here, we identified a SARS-CoV-2-driven membrane structure named the 3a dense body (3DB). 3DBs are unusual electron-dense and dynamic structures driven by the accessory protein ORF3a via remodeling a specific subset of the trans-Golgi network (TGN) and early endosomal membrane. 3DB formation is conserved in related bat and pangolin coronaviruses but was lost during the evolution to SARS-CoV. During SARS-CoV-2 infection, 3DB recruits the viral structural proteins spike (S) and membrane (M) and undergoes dynamic fusion/fission to maintain the optimal unprocessed-to-processed ratio of S on assembled virions. Disruption of 3DB formation resulted in virions assembled with an abnormal S processing rate, leading to a dramatic reduction in viral entry efficiency. Our study uncovers the crucial role of 3DB in maintaining maximal SARS-CoV-2 infectivity and highlights its potential as a target for COVID-19 prophylactics and therapeutics.

Suggested Citation

  • Stella Hartmann & Lisa Radochonski & Chengjin Ye & Luis Martinez-Sobrido & Jueqi Chen, 2025. "SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59475-x
    DOI: 10.1038/s41467-025-59475-x
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