Formation of aggresome-like structures in herpes simplex virus type 2-infected cells and a potential role in virus...

Herpes simplex virus (HSV) is a large, enveloped DNA virus that replicates in the nucleus and is assembled in the cytoplasm to the mature infectious virion. In this study, we present evidence that, in HSV-2-infected cells, some tegument proteins (UL46 and VP16) and newly synthesized nucleocapsids accumulate in a juxtanuclear domain sharing characteristics with aggresomes, cellular structures formed in response to misfolded proteins [J. Cell Biol. 146 (1999) 1239, J. Cell Biol. 143 (1998) 2010]. The juxtanuclear domains (aggresome-like structures) induced by HSV-2 infection localize to the microtubule organizing center (MTOC) where the clustering mitochondria, Golgi-derived vesicles, and cellular chaperones including heat shock protein (Hsp)40 and Hsp70 were recruited. Formation of aggresome-like structures was blocked by the presence of microtubule-disassembling drug nocodazole, indicating that microtubule-dependent transport may be involved in the accumulation of viral and cellular proteins at these sites in HSV-2-infected cells. These features are similar to those governing the formation of aggresomes. In contrast to aggresomes, however, the vimentin cage surrounding the MTOC was not observed with the aggresome-like structures in HSV-2-infected cells, and the maintenance of these structures required an intact microtubular network. Disruption of the aggresome-like structures by nocodazole treatment led to a low but consistent effect (10-fold decrease) on the production of intracellular infectious particles. These results suggest that aggresome-like structures do not play a critical but augmentary role in HSV-2 replication.