Waltmann C, Asor R, Raviv U, Olvera de la Cruz M. Assembly and Stability of Simian Virus 40 Polymorphs. ACS Nano [Internet]. 2020;14 (4) :4430-4443. Publisher's Version
Asor R, Schlicksup CJ, Zhao Z, Zlotnick A, Raviv U. Rapidly Forming Early Intermediate Structures Dictate the Pathway of Capsid Assembly. Journal of the American Chemical Society [Internet]. 2020; 142 (17) :7868–7882. Publisher's Version
Asor R, Khaykelson D, Ben-nun-Shaul O, Levi-Kalisman Y, Oppenheim A, Raviv U. pH Stability and Disassembly Mechanism of Wild-Type Simian Virus 40. Soft Matter [Internet]. 2020;16 (11) :2803-2814. Publisher's VersionAbstract

Virus are remarkable self-assembled nanobiomaterial-based machines, exposed to a wide range of pH values. Extreme pH values can induce dramatic structural changes, critical for the function of the virus nanoparticles including assembly and genome uncoating. Tuning cargo - capsid interactions is essential for designing viral-based delivery systems. Here we show how pH controls the structure and activity of wild-type simian virus 40 (wtSV40) and the interplay between its cargo and capsid. Using cryo-TEM and solution X-ray scattering, we found that wtSV40 was stable between pH 5.5 and 9, and only slightly swelled with increasing pH. At pH 3, the particles aggregated, while capsid protein pentamers continued to coat the virus cargo but lost their positional correlations. Infectivity was only partly lost after the particles had been returned to pH 7. At pH 10 or higher, the particles were unstable, lost their infectivity, and disassembled. Using time-resolved experiments we discovered that disassembly began by swelling of the particles, poking a hole in the capsid through which the genetic cargo escaped, and followed by a slight shrinking of the capsids and complete disassembly. These findings provide insight into the fundamental intermolecular forces, essential for SV40 function, and for designing virus-based nanobiomaterials, including delivery systems and antiviral drugs.

Khaykelson D, Raviv U. Studying viruses using solution X-ray scattering. Biophysical Reviews [Internet]. 2020;12 :41–48. Publisher's VersionAbstract

Viruses have been of interest to mankind since their discovery as small infectious agents in the nineteenth century. Because many viruses cause diseases to humans and agriculture, they were rigorously studied for biological and medical purposes. Viruses have remarkable properties such as the symmetry and self-assembly of their protein envelope, maturation into infectious virions, structural stability, and disassembly. Solution X-ray scattering can probe structures and reactions in solutions, down to subnanometer spatial resolution and millisecond temporal resolution. It probes the bulk solution and reveals the average shape and average mass of particles in solution and can be used to study kinetics and thermodynamics of viruses at different stages of their life cycle. Here we review recent work that demonstrates the capabilities of solution X-ray scattering to study in vitro the viral life cycle.

Asor R, Selzer L, Schlicksup CJ, Zhao Z, Zlotnick A, Raviv U. Assembly Reactions of Hepatitis B Capsid Protein into Capsid Nanoparticles Follow a Narrow Path Through a Complex Reaction Landscape. ACS Nano [Internet]. 2019;13 (7) :7610-7626. Publisher's Version
Zhao Z, Che-Yen Wang J, Gonzalez-Gutierrez G, Venkatakrishnan B, Asor R, Khaykelson D, Raviv U, Zlotnick A. Structural differences between the Woodchuck hepatitis virus core protein in dimer and capsid states are consistent with entropic and conformational regulation of assembly. Journal of Virology [Internet]. 2019 :JVI.00141-19. Publisher's Version
Asor R, Khaykelson D, Ben-nun-Shaul O, Oppenheim A, Raviv U. Effect of Calcium Ions and Disulfide Bonds on Swelling of Virus Particles. ACS Omega [Internet]. 2019;4 (1) :58–64. Publisher's Version
Asor R, Ben-nun-Shaul O, Oppenheim A, Raviv U. Crystallization, Reentrant Melting, and Resolubilization of Virus Nanoparticles. ACS Nano [Internet]. 2017;11 (10) :9814-9824. Publisher's Version
Saper G, Kler S, Asor R, Oppenheim A, Raviv U, Harries D. Effect of capsid confinement on the chromatin organization of the SV40 minichromosome. Nucleic acids research [Internet]. 2013;41 (3) :1569-1580. Publisher's Version
Kler S, Asor R, Li C, Ginsburg A, Harries D, Oppenheim A, Zlotnick A, Raviv U. RNA encapsidation by SV40-derived nanoparticles follows a rapid two-state mechanism. Journal of the American Chemical Society [Internet]. 2012;134 (21) :8823-8830. Publisher's Version