Herpes simplex virus type 1 abrogates the antiviral activity of Ch25h via its virion host shutoff protein

Antiviral Res. 2017 Jul:143:69-73. doi: 10.1016/j.antiviral.2017.04.004. Epub 2017 Apr 9.

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.

Keywords: Ch25h; HSV-1; vhs/UL41.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Gene Expression Regulation, Viral
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Herpes Simplex / drug therapy
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 1, Human / pathogenicity
  • Humans
  • RNA, Messenger / genetics
  • Steroid Hydroxylases / genetics
  • Steroid Hydroxylases / pharmacology*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virion / drug effects*
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • RNA, Messenger
  • Ul41 protein, Human herpesvirus 1
  • Viral Proteins
  • Steroid Hydroxylases
  • cholesterol 25-hydroxylase