Structural analysis of herpes simplex virus by optical super-resolution imaging

Laine, Romain F.; Albecka, Anna; van de Linde, Sebastian; Rees, Eric J.; Crump, Colin M.; Kaminski, Clemens F.

Although interpretation is not as straightforward as for the shell diameter data, the shell thickness also provides structural information. For instance, as the gD protein layer is part of the membrane structure (with no intrinsic thickness), the large thickness obtained for gD (40 nm) indicates a large variability of the envelope diameter from particle to particle (supporting the large range of particle sizes found by EM) and/or a potential deviation from the spherical symmetry, underlying the plasticity of the envelope. On the other hand, the thickness of VP16 and pUL37 appear smaller than that of gD, which is consistent with the notion that there is much less plasticity in the virus tegument compared with the envelope layer. At the moment, we do not have a clear explanation as to the observed differences in the thickness for VP1/2 and pUL37. Reasons could include differential labelling efficiencies for the two proteins and dense packing of fluorophores on the small shell of VP1/2, increasing localization artefacts. An underestimation of the alignment error would also lead to an overestimation of the shell thickness (see Supplementary Note 4). Finally, there may be differential 'plasticity' of the two protein layers, leading to a real geometric distortion.