Dynamic Self-Assembly of Virus Capsids

The assembly and disassembly of virus capsids, composed of many subunits, are fundamental steps in the viral life cycle. The complete set of possible capsid intermediates is immense, yet the concerted assembly process is done with high fidelity and leads to stable capsids that can efficiently encapsulate and protect genetic material, and when needed, dissociate and release their cargo. Virus capsids are therefore stable and flexible dynamic structures. To better understand and predict the outcomes of these apparently contradictory processes, we precisely analyzed the structure, kinetics, and thermodynamic stability of the experimentally tractable virus assembly reaction, in vitro. High-resolution modern synchrotron solution X-ray scattering measurements of assembly reactions provided statistically reliable and rich structural data. We rigorously analyzed the data by integrating our home-developed state-of-the-art scattering data analysis software D+ (https://scholars.huji.ac.il/uriraviv/software/d-software) with simulations and theory of macromolecular self-assembly. Our accurate and comprehensive analysis provided new insight into the mechanisms of viral self-assembly and the boundaries where thermodynamic products can be realized and function, and when kinetically trapped metastable states may form. This insight could be important for designing antiviral therapeutics as well as noncapsules or nanoreactors.

(Israel Science Foundation (Grant 656/17), NIH (Award Number 1R01AI118933.