HOW LARGE MOLECULES CAN ENTER CELL
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| Year of publication | 2022 |
| Type | Conference abstract |
| MU Faculty or unit | |
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| Description | Various endocytic pathways have evolved to tightly regulate the vital internalization of large molecules into cells. However, viruses can hijack these processes to enter their hosts. After the interaction between the virus and membrane receptors, the plasma membrane is bent and wrapped around the virus. Once the wrapping is completed, the virus is internalized in the endosome. We have shown that such wrapping could be a spontaneous process, i.e., not requiring ATP, and its efficacy depends on the virus size, shape, and coverage of binding sites1,2. This pathway is not limited to viruses and could be utilized by nanoparticles and other drug carriers. Later in the cell, viruses need to release their content into the cell. This release was previously assumed to occur via tiny pores/openings observed in non-enveloped RNA virus structures. However, such a release would be slow, requiring the unwinding of putative double-stranded segments and enabling genome degradation. We have recently combined cryo-electron microscopy and computer simulations to demonstrate an alternative release mechanism in which the capsid cracks open, and the genome rapidly releases via a large opening3,4. This release was triggered by decreased pH in vitro, and self-reassembled capsids were found to occasionally miss one or few capsid-protein pentamers after the release. The shape and extent of the opening were determined to depend primarily on the interaction range between the pentamers5. These findings uncover molecular details of virus entry and genome release that could be utilized in the development of antiviral drugs or nanoparticles for drug delivery. |
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