AUTHOR=Qin Shurong , Hu Xiao , Lin Shimin , Xiao Ji , Wang Zhaoyang , Jia Jiaoyan , Song Xiaowei , Liu Kaisheng , Ren Zhe , Wang Yifei 

TITLE=Hsp90 Inhibitors Prevent HSV-1 Replication by Directly Targeting UL42-Hsp90 Complex

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 12 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.797279

DOI=10.3389/fmicb.2021.797279

ISSN=1664-302X

ABSTRACT=Herpes simplex virus type I (HSV-1) is a member of the Alphaherpesvirinae family, which could initiate labial herpes caused by the reactivation of HSV-1 primary infection, and genital herpes caused by secondary infection even causes herpes encephalitis. The study presented here demonstrates that new Hsp90 inhibitors AT-533 and 17-AAG directly prevent the replication of HSV-1 without affecting RNA transcription. Other mechanisms revealed that Hsp90 inhibitors (AT-533 and 17-AAG) directly targeted the HSV-1 UL42-Hsp90 complex, and Hsp90 interacted with HSV-1 UL42 in silicon and experiment. Interestingly, Hsp90 inhibitors also reduced ACV-resistant clinical HSV-1 strains (153 and blue strain) virus titers and DNA copy numbers, revealing that HSV-1 UL42 would be a new target against ACV-resistant HSV-1 strains. Altogether, this present study indicates that Hsp90 inhibitors prevent HSV-1 replication by regulating the interaction between Hsp90 and HSV-1 UL42 and suggests a promising target for anti-HSV-1 therapies in the replication.