Viperin has species-specific roles in response to herpes simplex virus infection

J Gen Virol. 2021 Aug;102(8):001638. doi: 10.1099/jgv.0.001638.


Viperin is a gene with a broad spectrum of antiviral functions and various mechanisms of action. The role of viperin in herpes simplex virus type 1 (HSV-1) infection is unclear, with conflicting data in the literature that is derived from a single human cell type. We have addressed this gap by investigating viperin during HSV-1 infection in several cell types, spanning species and including immortalized, non-immortalized and primary cells. We demonstrate that viperin upregulation by HSV-1 infection is cell-type-specific, with mouse cells typically showing greater increases compared with those of human origin. Further, overexpression and knockout of mouse, but not human viperin significantly impedes and increases HSV-1 replication, respectively. In primary mouse fibroblasts, viperin upregulation by infection requires viral gene transcription and occurs in a predominantly IFN-independent manner. Further we identify the N-terminal domain of viperin as being required for the anti-HSV-1 activity. Interestingly, this is the region of viperin that differs most between mouse and human, which may explain the apparent species-specific activity against HSV-1. Finally, we show that HSV-1 virion host shutoff (vhs) protein is a key viral factor that antagonises viperin in mouse cells. We conclude that viperin can be upregulated by HSV-1 in mouse and human cells, and that mouse viperin has anti-HSV-1 activity.

Keywords: HSV; herpes simplex virus; innate immunity; species-specificity; viperin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / immunology
  • Cell Line
  • Chlorocebus aethiops
  • Fibroblasts / cytology
  • Fibroblasts / immunology
  • Herpes Simplex* / immunology
  • Herpes Simplex* / virology
  • Herpesvirus 1, Human / immunology*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Oxidoreductases Acting on CH-CH Group Donors
  • Proteins / physiology*
  • Ribonucleases / immunology
  • Viral Proteins / immunology


  • Antiviral Agents
  • Proteins
  • Rsad2 protein, mouse
  • Viral Proteins
  • virion host shutoff protein, Simplexvirus
  • Oxidoreductases Acting on CH-CH Group Donors
  • RSAD2 protein, human
  • Ribonucleases