A Super-Resolution Spatial Atlas of SARS-CoV-2 Infection in Human Cells

Area of Science:

• Virology
• Cell Biology
• Structural Biology

Background:

• The spatial organization of viral and host factors is critical for infection dynamics.
• The nanoscale architecture of SARS-CoV-2 replication organelles is not well understood.

Purpose of the Study:

• To create a comprehensive super-resolution spatial atlas of SARS-CoV-2 infection in human cells.
• To systematically map the localization of viral proteins and RNAs during infection.

Main Methods:

• Super-resolution microscopy
• High-resolution imaging of viral and host components
• Localization studies of viral proteins and RNAs

Main Results:

• The viral main protease (nsp5) localizes within double-membrane vesicles (DMVs), suggesting late-stage polyprotein processing.
• Novel structures including dsRNA "connectors" linking DMVs and dsRNA granules with replicase components were identified.
• The antiviral nirmatrelvir promotes the formation of persistent bodies of uncleaved polyproteins.

Conclusions:

• The spatial atlas provides a foundational resource for understanding SARS-CoV-2 biology.
• Findings offer new insights into viral replication, assembly, and the mechanism of antiviral drugs like nirmatrelvir.