Impact of dynamin 2 on adenovirus nuclear entry.

Abstract

The large GTPase dynamin 2 controls both endosomal fission and microtubule acetylation. Here we report that dynamin 2 alters microtubules and regulates the trafficking of human adenovirus type 37. Dynamin 2 knockdown by siRNA in infected cells resulted in accumulation of acetylated tubulin, repositioning of microtubule organizing centers (MTOCs) closer to cell nuclei, increased virus in the cytosol (with a compensatory decrease in endosomal virus), reduced proinflammatory cytokine induction, and increased binding of virus to the nucleoporin, Nup358. These events led to increased viral DNA nuclear entry and viral replication. Overexpression of dynamin 2 generated opposite effects. Therefore, dynamin 2 inhibits adenovirus replication and promotes innate immune responses by the infected cell. MTOC transposition in dynamin 2 knockdown promotes a closer association with nuclear pore complexes to facilitate viral DNA delivery. Dynamin 2 plays a key role in adenoviral trafficking and influences host responses to infection.

• Authors: Ji Sun Lee, Ashrafali M Ismail, Jeong Yoon Lee, Xiaohong Zhou, Emma C Materne, James Chodosh, Jaya Rajaiya
• Journal: Virology (Virology) Vol. 529 Pg. 43-56 (03 2019) ISSN: 1096-0341 [Electronic] United States
• PMID: 30660774 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Dynamin II

Topics

• Adenoviridae (physiology)
• Cytosol (physiology)
• Dynamin II (physiology)
• Gene Knockdown Techniques
• Humans
• Virus Internalization
• Virus Replication (physiology)