Cryomicroscopy of human cytomegalovirus virions reveals move densely packed genomic DNA than in herpes simplex virus type 1

All members of the herpesvirus family have a characteristic virion structur e, comprising a DNA containing, icosahedral capsid, embedded in a proteinac eous layer (tegument) and surrounded by a lipid envelope. Human cytomegalov irus (HCMV, the prototypic P-herpesvirus) has a genome that is significantl y larger (>50 %) than that of the a-herpesvirus HSV-1. Although the interna l volume of the HCMV capsid is approximately 17% larger than that of HSV-1, this slight increase in volume does not provide adequate space to encapsid ate the full length HCMV genome at the same packing density as HSV-1. We have investigated the nature of DNA packing in HCMV and HSV-1 virions by electron-croyomicroscopy and image processing. Radial density profiles cal culated from projection images of HCMV and HSV-1 capsids suggest that there is no increase in the volume of the HCMV capsid upon DNA packaging. Packin g density of the viral DNA was assessed for both HCMV and HSV-1 by image an alysis of both full and empty particles. Our results for packing density in HSV-I are in good agreement with previously published measurements, showin g an average inter-layer spacing of approximately 26 Angstrom. Measurements taken from our HCMV images, however, suggest that the viral genomic DNA is more densely packed, with an average inter-layer spacing of approximately 23 Angstrom. We propose therefore, that the combination of greater volume i n HCMV capsids and increased packing density of viral DNA accounts for its ability to encapsidate a large genome. (C) 2000 Academic Press.