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Comparative Virus-Host Protein Interactions of the Bluetongue Virus NS4 Virulence Factor. | LitMetric

Comparative Virus-Host Protein Interactions of the Bluetongue Virus NS4 Virulence Factor.

Viruses

UMR VIROLOGIE, INRAE, École Nationale Vétérinaire d'Alfort, ANSES Laboratoire de Santé Animale, Université Paris-Est, 94700 Maisons-Alfort, France.

Published: January 2022

AI Article Synopsis

  • Bluetongue virus (BTV) causes a range of disease symptoms in ruminants, from mild to severe, but the exact factors behind its virulence are not fully understood.
  • Researchers used a yeast two-hybrid screening approach to identify cellular targets of the NS4 protein from two BTV serotypes, BTV8 and BTV27, discovering that Wilms' tumor 1-associated protein (WTAP) interacts specifically with BTV8's NS4.
  • The interaction is crucial for viral replication, as silencing WTAP decreases both viral titers and the production of viral proteins, indicating that BTV-NS4 uses WTAP to enhance its infectious process.

Article Abstract

Bluetongue virus (BTV) is the etiologic agent of a non-contagious arthropod-borne disease transmitted to wild and domestic ruminants. BTV induces a large panel of clinical manifestations ranging from asymptomatic infection to lethal hemorrhagic fever. Despite the fact that BTV has been studied extensively, we still have little understanding of the molecular determinants of BTV virulence. In our report, we have performed a comparative yeast two-hybrid (Y2H) screening approach to search direct cellular targets of the NS4 virulence factor encoded by two different serotypes of BTV: BTV8 and BTV27. This led to identifying Wilms' tumor 1-associated protein (WTAP) as a new interactor of the BTV-NS4. In contrast to BTV8, 1, 4 and 25, NS4 proteins from BTV27 and BTV30 are unable to interact with WTAP. This interaction with WTAP is carried by a peptide of 34 amino acids (NS4) within its putative coil-coiled structure. Most importantly, we showed that binding to WTAP is restored with a chimeric protein where BTV27-NS4 is substituted by BTV8-NS4 in the region encompassing residue 22 to 55. We also demonstrated that WTAP silencing reduces viral titers and the expression of viral proteins, suggesting that BTV-NS4 targets a cellular function of WTAP to increase its viral replication.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878768PMC
http://dx.doi.org/10.3390/v14020182DOI Listing

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