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

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 secondary infection even causes herpes encephalitis. The study presented here demonstrates 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 virus titers of ACV-resistant clinical HSV-1 strains (153 and blue strain), 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 proliferation by regulating the interaction between Hsp90 and HSV-1 UL42, suggesting a promising target for anti-HSV-1 therapies in the replication.