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Abstract

The shortcomings of current direct-acting anti-viral therapy against human cytomegalovirus (HCMV) has led to interest in host-directed therapy. Here we re-examine the use of interferon proteins to inhibit HCMV replication utilizing both high and low passage strains of HCMV. Pre-treatment of cells with interferon alpha (IFNα) was required for robust and prolonged inhibition of both low and high passage HCMV strains, with no obvious toxicity, and was associated with an increased anti-viral state in HCMV-infected cells. Pre-treatment of cells with IFNα led to poor expression of HCMV immediate-early proteins from both high and low passage strains, which was associated with the presence of the anti-viral factor SUMO-PML. Inhibition of HCMV replication in the presence of IFNα involving ZAP proteins was HCMV strain-dependent, wherein a high passage HCMV strain was obviously restricted by ZAP and a low passage strain was not. This suggested that strain-specific combinations of anti-viral factors were involved in inhibition of HCMV replication in the presence of IFNα. Overall, this work further supports the development of strategies involving IFNα that may be useful to inhibit HCMV replication and highlights the complexity of the anti-viral response to HCMV in the presence of IFNα.

Funding
This study was supported by the:
  • Wellcome Trust (Award WT098049AIA)
    • Principle Award Recipient: StuartNeil
  • Medical Research Council (Award MR/S00971X/1)
    • Principle Award Recipient: RichardStanton
  • Medical Research Council (Award MR/W025647/1)
    • Principle Award Recipient: MichaelWeekes
  • Medical Research Council (Award MR/W018519/1)
    • Principle Award Recipient: ChadSwanson
  • Medical Research Council (Award MR/S000844/1)
    • Principle Award Recipient: StuartNeil
  • Medical Research Council (Award MR/W006677/1)
    • Principle Award Recipient: KatieLatham
  • 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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/content/journal/jgv/10.1099/jgv.0.001929
2023-12-08
2025-02-08
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