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

Naoki Nozawa, Yohei Yamauchi, Kenzo Ohtsuka, Yasushi Kawaguchi, Yukihiro Nishiyama

Research output: Contribution to journalArticle (Academic Journal)

43 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)486-97
Number of pages12
JournalExperimental Cell Research
Volume299
Issue number2
DOIs
Publication statusPublished - 1 Oct 2004

Keywords

  • Animals
  • Antineoplastic Agents
  • Biological Transport
  • Cercopithecus aethiops
  • Gene Expression Regulation
  • Herpesvirus 2, Human
  • Microtubule-Organizing Center
  • Microtubules
  • Nocodazole
  • Organelles
  • Vero Cells
  • Vimentin
  • Viral Structural Proteins
  • Virus Assembly
  • Virus Replication
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't

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