Virusmediated Centrosomal Damage

In a small number of cases, virus infection has been shown to result in almost complete ablation of the centrosome. In vaccinia-infected cells, centrosome destruction is characterized by a rapid loss of centrosomal proteins from the MTOC as determined by immunofluorescence, and starts from 2 h post-infection (Figure 19.4). This effect appears to be due to a redistribution of proteins within the cell, since levels of expressed centrosomal proteins, measured by Western blot, are not significantly reduced over the same period. The ability of the centro-some to re-nucleate microtubules is also greatly diminished by vaccinia infection.

Figure 19.4 Vaccinia infection damages the centrosome. Centrosomes in vaccinia-infected cells show dramatically reduced labelling with antibodies against centrosomal proteins including gamma-tubulin (A-D), pericentrin (E, F), C-Nap1 (G, H) and centrin (K, L). Reproduced from [9] with permission from Oxford University Press.

Figure 19.4 Vaccinia infection damages the centrosome. Centrosomes in vaccinia-infected cells show dramatically reduced labelling with antibodies against centrosomal proteins including gamma-tubulin (A-D), pericentrin (E, F), C-Nap1 (G, H) and centrin (K, L). Reproduced from [9] with permission from Oxford University Press.

Centrosome destruction also appears to require the expression of viral genes, although the gene responsible has not been identified [9].

More recently, centrosome destruction was also observed in HSV-1-infected cells, where VP22-dependent microtubule reorganization may be involved. In this case, MTOCs have been shown to return after prolonged infection, suggesting that the process of destruction is reversible [58]. Centrosomal defects have also been described by electron microscopy in cytomegalovirus (CMV)-infected cells, where disruption of centriole structure and detachment of fibrillar material occur [59]. Whether these changes are also seen during vaccinia- or HSV-1-mediated centro-some destruction, and so represent a general response to a variety of different viral infections, remains to be seen.

Centrosome destruction was first observed many years ago, as a cellular response to heat shock [60]. Both viral infection and heat shock are potent activators of stress pathways, raising the intriguing possibility that centrosome stability is under the control of stress-activated signaling [61]. Centrosomal damage may therefore be an underlying cause of microtubule reorganization in many other viral infections, since in many cases the centrosome has been overlooked when characterizing virus-induced alterations in the microtubule network.

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