Human bone marrow fibroblasts infected by cytomegalovirus: Ultrastructural observations

Human cytomegalovirus (HCMV) is capable of infecting human bone marrow fibroblastic stromal cells (HBMF-sc). This infection is important to assess in regard to the pathogenesis of HCMV, particularly in immunocompromised patients. Stromal fibroblastic cells were infected by Towne strain of cytomegalovirus (CMV) in vitro. Several ultrastructural features of uninfected HBMF-sc were also described. The CMV-infected cells exhibited significant mitochondrial enlargement, production of dense bodies by the Golgi apparatus and cytoplasmic accumulation. Ultrastructural aspects of HCMV entry in host cells, capture by endosomes, penetration of genetic material in the nucleoplasm, assembly and formation of nucleocapsids were detected and described. Viral fusion and transit through the nuclear envelope were shown along with envelope proliferations. Trafficking of virions, maturation and completion of their cytoplasmic coating were also illustrated. Fully developed virions, defective virions, other apparently-emptied vesicles, multivesicular bodies as well as cytoplasmic dense bodies were illustrated along arrays of microtubules organized by defective centrosomes and constituted a peculiar structure that we termed 'viral field'. While some viral and dense bodies were carried to adjacent sites of the plasmalemma, in order to be extruded from the infected cells, others were concentrated into black holes-dense heterogenous bodies accumulated at the periphery of viral fields. This study further described the functional aspects of HBMF-sc and summarized the unknown aspects of ultrastructural characteristics of HCMV-infected fibroblastic stromal cells which may serve as harmful reservoir for the replication of virus. In addition, the findings of this study may stimulate further investigations about the basic cell biology and functions of the bone marrow stromal cells and may also generate some interests to bone marrow transplantation medicine as to how HBMF-sc can serve as a reservoir in the pathogenesis of CMV infections.