We investigated the ultrastructural development and maturation of cytomegalovirus (CMV) nuclear inclusions (NIs) in human embryo thyroid cells at 1 to 144 h post-infection. At 5 h, most cells had rounded from an initial fibroblastic appearance and contained early NIs. At 24 h, early NIs were larger and better defined. At 48 h, although early NIs were still present, most cells had larger and presumably more mature NIs. These latter NIs consisted of several subunits, each made up of a fibrillar network enclosing an electron-lucent area which contained coarse and delicate granules. Also, at 48 h, virus particles were first seen in the nucleoplasm. At 72 h, in cells with more developed NIs, virus particles were closely associated with the fibrillar network. Between 96 and 144 h, the NIs reached maximum size and were made up of numerous subunits. The results indicate that two types of NIs coexist during CMV infection. The appearance of the early and late NIs coincides with the reported peaks of CMV DNA synthesis and thus may explain the biphasic pattern of DNA synthesis in CMV infection. Morphogenetic features of the NIs conform with the hypothesis that synthesis of CMV DNA may occur in the centre of each NI subunit and that the fibrillar network represents condensing capsid proteins.


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