1887

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Volume 102, Issue 8

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

Abstract

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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): herpes simplex virus , HSV , innate immunity , species-specificity and viperin
Funding
This study was supported by the:
  • australian research council (Award DP190101325)
    • Principle Award Recipient: DavidC Tscharke
  • national health and medical research council (Award GNT1126599)
    • Principle Award Recipient: DavidC Tscharke
  • national health and medical research council (Award GNT1162025)
    • Principle Award Recipient: SiMing Man
  • national health and medical research council (Award GNT1104329)
    • Principle Award Recipient: DavidC Tscharke
© 2021 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2021-08-18
2024-04-25
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Viperin has species-specific roles in response to herpes simplex virus infection
J. Gen. Virol. 102, 001638 (2021); https://doi.org/10.1099/jgv.0.001638
/content/journal/jgv/10.1099/jgv.0.001638
/content/journal/jgv/10.1099/jgv.0.001638
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