1 Cellular protein TTC4 and its cofactor HSP90 are pro-viral for bovine herpesvirus 1

Beth H Thompson, Colin Sharp, Inga Dry, Robert Dalziel, Eleanor Gaunt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Bovine Herpesvirus Type 1 (BoHV-1) infection causes infectious bovine rhinotracheitis and genital disease in cattle, with significant economic and welfare impacts. However, the role of cellular host factors during viral replication remains poorly characterised. A previously performed genome-wide CRISPR knockout screen identified pro- and antiviral host factors acting during BoHV-1 replication. Herein we validate a pro-viral role for a candidate from this screen: the cellular protein tetracopeptide repeat protein 4 (TTC4). We show that TTC4 transcript production is upregulated during BoHV-1 infection. Depletion of TTC4 protein impairs BoHV-1 protein production but does not reduce production of infectious virions, whereas overexpression of exogenous TTC4 results in a significant increase in production of infectious BoHV-1 virions. TTC4 itself is poorly characterized (especially in the context of virus infection), but is a known co-chaperone of heat shock protein 90 (HSP90). HSP90 has a well-characterized pro-viral role during the replication of diverse herpesviruses, and we therefore hypothesized that HSP90 is also pro-viral for BoHV-1. Drug-mediated inhibition of HSP90 using geldanamycin at sub-cytotoxic concentrations inhibited both BoHV-1 protein production and viral genome replication, indicating a pro-viral role for HSP90 during BoHV-1 infection. Our data demonstrates pro-viral roles for both TTC4 and HSP90 during BoHV-1 replication; possibly, interactions between these two proteins are required for optimal BoHV-1 replication, or the two proteins may have independent pro-viral roles.
Original languageEnglish
Article number198927
JournalVirus Research
Early online date10 Sept 2022
Publication statusPublished - Nov 2022

Keywords / Materials (for Non-textual outputs)

  • Bovine herpesvirus 1
  • tetracopeptide repeat protein 4 (TTC4)
  • heat shock protein 90 (HSP90)
  • geldanamycin


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