title: Herpes simplex virus type 1 abrogates the antiviral activity of Ch25h via its virion host shutoff protein.
abstract: Cholesterol 25-hydroxylase (Ch25h) is an interferon-inducible protein, and recent studies have demonstrated that it inhibited the replication of many enveloped viruses. However, in this study, we found that cells infected with wild-type (WT) HSV-1 reduced the expression of Ch25h, and ectopic expression of Ch25h could not inhibit the replication of WT-HSV-1. By screening assay, HSV-1 UL41 protein was found to down-regulate the expression of Ch25h. In addition, UL41 abrogated the antiviral activity of Ch25h via degrading its mRNA. Furthermore, ectopic expression of Ch25h inhibited the replication of UL41-null mutant HSV-1 (R2621), but not WT-HSV-1, and knockdown of Ch25h did not affect the replication of WT-HSV-1, but promoted the replication of the R2621. For the first time, HSV-1 UL41 was demonstrated to evade the antiviral function of Ch25h via its endonuclease activity.
authors.affiliation: Soochow University, Institutes of Biology and Medical Sciences, Suzhou 215123, China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: You
authors.affiliation: Soochow University, Institutes of Biology and Medical Sciences, Suzhou 215123, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yuan
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University, Xiamen, 361102, China.
authors.forename: Wenkun
authors.initials: W
authors.lastname: Fu
authors.affiliation: Soochow University, Institutes of Biology and Medical Sciences, Suzhou 215123, China.
authors.forename: Chenhe
authors.initials: C
authors.lastname: Su
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University, Xiamen, 361102, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University, Xiamen, 361102, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Cheng
authors.affiliation: Soochow University, Institutes of Biology and Medical Sciences, Suzhou 215123, China; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, T2N 4N1, Canada. Electronic address: zheng.alan@hotmail.com.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Zheng
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006561:Herpes Simplex / Q000188:drug therapy; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics / Q000494:pharmacology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D012333:RNA, Messenger; C081688:Ul41 protein, Human herpesvirus 1; D014764:Viral Proteins; D013250:Steroid Hydroxylases; C507384:cholesterol 25-hydroxylase
keywords: Ch25h; HSV-1; vhs/UL41