title: Ubiquitin-proteasome-dependent slingshot 1 downregulation in neuronal cells inactivates cofilin to facilitate HSV-1 replication.
abstract: Actin and its regulators are critical for neuronal function. Infection with herpes simplex virus 1 (HSV-1) remodels neuronal cell actin dynamics, which may relate virus-induced pathological processes in the nervous system. We previously demonstrated that cofilin is an actin regulator that participates in HSV-1-induced actin dynamics in neuronal cells, but how HSV-1 regulates cofilin has remained unclear. In the present study, we demonstrated the HSV-1-induced the inactivation of cofilin and the accumulation of phosphorylated cofilin in the nucleus, which together benefited viral replication. This consistent cofilin inactivation was achieved by the downregulation of slingshot 1 (SSH1). Notably, virus-induced SSH1 downregulation depended on the ubiquitin-proteasome system. Cofilin inactivation is therefore critical for HSV-1 replication during neuronal infection and is maintained by SSH1 downregulation. Moreover, these results provide new insight into the HSV-1-induced neurological pathogenesis and suggest potential new strategies to inhibit HSV-1 replication.
authors.affiliation: Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632, China; College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Yangfei
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zheng
authors.affiliation: Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632, China; College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Meigong
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632, China; College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632, China.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632, China.
authors.forename: Shaoxiang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo-City 409-3898, Japan.
authors.forename: Jianglin
authors.initials: J
authors.lastname: Fan
authors.affiliation: Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632, China. Electronic address: twang-yf@163.com.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Wang
mesh_terms: D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D051338:Cofilin 1 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006561:Herpes Simplex / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000821:virology*; D010749:Phosphoprotein Phosphatases; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D021381:Protein Transport; D025801:Ubiquitin / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D051338:Cofilin 1; D025801:Ubiquitin; D010749:Phosphoprotein Phosphatases; C484329:SSH1 protein, human; D046988:Proteasome Endopeptidase Complex
keywords: Cofilin; F-actin; HSV-1; LIM kinase-1; LIMK1; SSH1; Ubiquitin-proteasome; actin filaments; herpes simplex virus 1; p-cofilin; phosphorylated cofilin; slingshot-1