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

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journal contribution
posted on 14.09.2021, 02:49 by Yeu-Yang Tseng, Anjali Gowripalan, Sarah N Croft, Stewart A Smith, Karla HelbigKarla Helbig, Si Ming Man, David C Tscharke
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.

Funding

This work was funded by a Discovery Project grant from the Australian ARC to DCT and SMM (DP190101325); DCT and SMM are funded by fellowships from the Australian NHMRC (APP1104329 and APP1162025, respectively).

History

Publication Date

01/01/2021

Journal

JOURNAL OF GENERAL VIROLOGY

Volume

102

Issue

8

Article Number

ARTN 001638

Pagination

12p.

Publisher

MICROBIOLOGY SOC

ISSN

0022-1317

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