The palisade layer of the poxvirus core is composed of flexible A10 trimers.

Due to its asymmetric shape, size and compactness, the structure of the infectious mature virus (MV) of vaccinia virus (VACV), the best-studied poxvirus, remains poorly understood. Instead, subviral particles, in particular membrane-free viral cores, have been studied with cryo-electron microscopy. Here, we compared viral cores obtained by detergent stripping of MVs with cores in the cellular cytoplasm, early in infection. We focused on the prominent palisade layer on the core surface, combining cryo-electron tomography, subtomogram averaging and AlphaFold2 structure prediction. We showed that the palisade is composed of densely packed trimers of the major core protein A10. Trimers display a random order and their classification indicates structural flexibility. A10 on cytoplasmic cores is organized in a similar manner, indicating that the structures obtained in vitro are physiologically relevant. We discuss our results in the context of the VACV replicative cycle, and the assembly and disassembly of the infectious MV.

Biological Cardiac Tissue Effects of High-Energy Heavy Ions - Investigation for Myocardial Ablation.

Noninvasive X-ray stereotactic treatment is considered a promising alternative to catheter ablation in patients affected by severe heart arrhythmia. High-energy heavy ions can deliver high radiation doses in small targets with reduced damage to the normal tissue compared to conventional X-rays. For this reason, charged particle therapy, widely used in oncology, can be a powerful tool for radiosurgery in cardiac diseases. We have recently performed a feasibility study in a swine model using high doses of high-energy C-ions to target specific cardiac structures. Interruption of cardiac conduction was observed in some animals. Here we report the biological effects measured in the pig heart tissue of the same animals six months after the treatment. Immunohistological analysis of the target tissue showed (1.) long-lasting vascular damage, i.e. persistent hemorrhage, loss of microvessels, and occurrence of siderophages, (2.) fibrosis and (3.) loss of polarity of targeted cardiomyocytes and wavy fibers with vacuolization. We conclude that the observed physiological changes in heart function are produced by radiation-induced fibrosis and cardiomyocyte functional inactivation. No effects were observed in the normal tissue traversed by the particle beam, suggesting that charged particles have the potential to produce ablation of specific heart targets with minimal side effects.