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Volume 105, Issue 4

Translational arrest and mRNA decay are independent activities of alphaherpesvirus virion host shutoff proteins Open Access

Abstract

The herpes simplex virus 1 (HSV1) virion host shutoff (vhs) protein is an endoribonuclease that regulates the translational environment of the infected cell, by inducing the degradation of host mRNA via cellular exonuclease activity. To further understand the relationship between translational shutoff and mRNA decay, we have used ectopic expression to compare HSV1 vhs (vhsH) to its homologues from four other alphaherpesviruses – varicella zoster virus (vhsV), bovine herpesvirus 1 (vhsB), equine herpesvirus 1 (vhsE) and Marek’s disease virus (vhsM). Only vhsH, vhsB and vhsE induced degradation of a reporter luciferase mRNA, with poly(A)+   hybridization indicating a global depletion of cytoplasmic poly(A)+ RNA and a concomitant increase in nuclear poly(A)+ RNA and the polyA tail binding protein PABPC1 in cells expressing these variants. By contrast, vhsV and vhsM failed to induce reporter mRNA decay and poly(A)+ depletion, but rather, induced cytoplasmic G3BP1 and poly(A)+ mRNA- containing granules and phosphorylation of the stress response proteins eIF2α and protein kinase R. Intriguingly, regardless of their apparent endoribonuclease activity, all vhs homologues induced an equivalent general blockade to translation as measured by single-cell puromycin incorporation. Taken together, these data suggest that the activities of translational arrest and mRNA decay induced by vhs are separable and we propose that they represent sequential steps of the vhs host interaction pathway.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): alphaherpesviruses , BHV1 , EHV1 , endoribonuclease , G3BP1 , HSV1 , MDV , PABPC1 , poly(A)+ FISH , stress granules , vhs and VZV
Funding
This study was supported by the:
  • MRC (Award MR/T001038/1)
    • Principle Award Recipient: GillianElliott
  • BBSRC (Award BB/T007923/1)
    • Principle Award Recipient: GillianElliott
© 2024 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution 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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2024-04-04
2024-04-30
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Translational arrest and mRNA decay are independent activities of alphaherpesvirus virion host shutoff proteins
J. Gen. Virol. 105, 001976 (2024); https://doi.org/10.1099/jgv.0.001976
/content/journal/jgv/10.1099/jgv.0.001976
/content/journal/jgv/10.1099/jgv.0.001976
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