Deletion of the Envelope gene attenuates SARS-CoV-2 infection by altered spike localization and increased cell-to-cell transmission.

Deleting the Envelope (E) gene in SARS-CoV-2 attenuates infection in Vero E6 cells expressing human ACE2 and TMPRSS2 and in human epithelial lines, linked to altered Spike localization.

• Why it matters: Envelope is a conserved coronavirus structural protein, but its cell biology role in SARS-CoV-2 assembly, release, and host interactions is not fully defined.
• What they did: Using a bacterial artificial chromosome, the authors generated reporter SARS-CoV-2 with or without the E gene and compared replication, virion formation, and Spike distribution by microscopy and virology assays.
• The result: ΔE SARS-CoV-2 increased cell-surface Spike, reduced Spike incorporation into particles, promoted cell-to-cell transmission that evades neutralizing antibody inhibition, and reorganization of the ERGIC and Golgi; E trans-complementation partially restored S incorporation and cell-free transmission.

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