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Centrosome injury in cells infected with human cytomegalovirus
V B Bystrevskaya1, T V Lobova, V N Smirnov
1Cardiology Research Center, Institute of Experimental Cardiology, Moscow, Russia.
Abstract:
The organization of the mitotic apparatus was studied in human embryo lung fibroblasts (HEL) and Vero cells at 4 days postinfection with human cytomegalovirus (HCMV) strain AD 169. The bipolar spindle was detected by immunofluorescence in p72-positive mitotic cells exhibiting a regular or C-metaphase-like chromosome configuration. Electron-microscopic study of C-metaphase-like cells revealed alteration of the centrosome structure which is characterized by the following features: (1) breakdown of the diplosome, (2) separation of the fibrillar material from centrioles, and (3) disruption of the centriolar cylinder. The spindle pole in the aberrant mitotic cells consisted of one or several foci of microtubules converging on the fibrillar aggregates. There are not any signs of the nuclear envelope reconstruction found in mitotic cells with highly condensed scattered chromosomes. Unlike in HEL cells, viral particles were not detected in Vero cells. A question arises as to whether centrosome injury is an integral part of the events leading to cell death unrelated to the reproduction of HCMV.
Insights
Human cytomegalovirus (HCMV) infection disrupts the centrosome structure in dividing cells, leading to abnormal mitotic spindles. This damage may contribute to cell death, independent of viral replication.
Area of Science:
- Cell Biology
- Virology
- Microscopy
Background:
- Human cytomegalovirus (HCMV) is a common pathogen that can affect various cell types.
- The impact of HCMV on the host cell's mitotic apparatus, particularly the centrosome, is not fully understood.
Purpose of the Study:
- To investigate the effects of HCMV infection on the organization of the mitotic spindle and centrosome structure in human embryo lung (HEL) fibroblasts and Vero cells.
- To determine if centrosome alterations are associated with abnormal mitosis and potentially cell death during HCMV infection.
Main Methods:
- Immunofluorescence microscopy was used to detect the bipolar spindle in p72-positive mitotic cells.
- Electron microscopy was employed to examine the ultrastructure of centrosomes in C-metaphase-like cells.
- HEL and Vero cells were infected with HCMV strain AD 169.
Main Results:
- HCMV infection led to alterations in centrosome structure, including diplosome breakdown, separation of fibrillar material from centrioles, and disruption of the centriolar cylinder.
- Aberrant mitotic cells displayed spindle poles composed of microtubule foci converging on fibrillar aggregates.
- No signs of nuclear envelope reconstruction were observed in mitotic cells with scattered chromosomes.
- Viral particles were absent in infected Vero cells, unlike in HEL cells.
Conclusions:
- HCMV infection causes significant damage to the centrosome structure, resulting in abnormal mitotic spindle organization.
- The observed centrosome injury raises the possibility that it is an integral event in HCMV-induced cell death, potentially occurring independently of viral replication.