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J Biochem. 2018 Dec 1;164(6):397-406. doi: 10.1093/jb/mvy066.

Hsp90 inhibitor AT-533 blocks HSV-1 nuclear egress and assembly.

Author information

1
Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China.
2
International Ocular Surface Research Center and Institute of Ophthalmology, College of Medicine, Jinan University Medical School, Guangzhou, China.
3
School of Pharmaceutical Sciences, Health Science Center Shenzhen University, Shenzhen, China.
4
Key Laboratory of Virology of Guangzhou, Jinan University, Guangzhou, China.
5
Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China.

Abstract

Heat shock protein 90 (Hsp90) has been identified as an essential host factor for the infection and replication of several viruses, including HSV-1. Recent works have clearly shown that Hsp90 plays a role in the early stages of HSV-1 infection, including nuclear import and DNA replication. However, the role of Hsp90 in the late stages of HSV-1 infection remains unclear. In this study, we found that Hsp90 was up-regulated during late viral infection. Treatment with the Hsp90 inhibitor AT-533 significantly decreased the intracellular and extracellular virus titers, and strongly inhibited nucleocapsid egress from the nucleus. More detailed studies revealed that AT-533 inhibited the nuclear egress of the viral nucleocapsid by suppressing the expression and translocation of nuclear-associated proteins pUL31 and pUL34. In addition, we found that AT-533 hindered the assembly of virus particles possibly though affecting the localization of glycoproteins in the endoplasmic reticulum and Golgi apparatus. These results thus invoke a new role for Hsp90 in the nucleocapsid egress and viral maturation of HSV-1, and further promote the development of Hsp90 inhibitors as potential anti-HSV-1 drugs.

PMID:
30107464
DOI:
10.1093/jb/mvy066
[Indexed for MEDLINE]

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