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Replication Cycle of SARS-CoV-2 in 3D – “We Can Expect the Coronavirus to Become – Health News Today

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Infected cells were imaged by focused ion beam scanning electron microscopy, a powerful technique to reveal the organization of a cell at the subcellular level in 3D. In this image, a subvolume of one cell was segmented to display membrane-bound organelles (in grey) and double-membrane vesicles (in red) – a virus-specific compartment where the viral genome is replicated in large quantities. Credit: Julian Hennies/EMBL

Learning how SARS-CoV-2 highjacks host cell machineries will help to develop therapeutic strategies.

As the global coronavirus pandemic continues, scientists are not only trying to find vaccines and drugs to combat it, but also to continuously learn more about the virus itself. “By now we can expect the coronavirus to become seasonal,” explains Ralf Bartenschlager, professor in the Department of Infectious Diseases, Molecular Virology, at Heidelberg University. “Thus, there is an urgent need to develop and implement both prophylactic and therapeutic strategies against this virus.” In a new study, Bartenschlager, assisted by the Schwab team at EMBL Heidelberg and using EMBL’s Electron Microscopy Core Facility, performed a detailed imaging analysis to determine how the virus reprograms infected cells.

Cells that become infected by SARS-CoV-2 die rather quickly, within only 24 to 48 hours. This indicates that the virus harms the human cell in such a way that it is rewired and essentially forced to produce viral progeny. The main aim of the project was therefore to identify the morphological changes within a cell that are inherent to this reprogramming. “To develop drugs which suppress the viral replication and thereby the consequence of the infection, as well as the virus-induced cell death, is key to have a better understanding of the biological mechanisms driving the virus’ replication cycle,” explains Bartenschlager. The team used the imaging facilities at EMBL and state-of-the art imaging techniques to determine the 3D architecture of SARS-CoV-2-infected cells, as well as alterations of cellular architecture caused by the virus.

The team was able to create 3D reconstructions of whole cells and their subcellular compartments. “We are providing critical insights into virus-induced structural changes in the studied human cells,” explains Ralf Bartenschlager. The images revealed an obvious and massive change in the endomembrane systems of the infected cells – a system that enables the cell to define different compartments and sites. The virus induces membrane changes in such a way that it can produce its own replication organelles. These are mini replication compartments where the viral genome is amplified enormously. To do this, the virus requires membrane surfaces. These are created by exploiting a cellular membrane system and creating an organelle, which has a very distinct appearance. The scientists describe it as a massive accumulation of bubbles: two membrane layers forming a big balloon. Within…

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