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African swine fever virus protein CP204L is involved in endosomal trafficking and interacts with the VPS39 subunit of the HOPS complex

ABSTRACT: African swine fever virus (ASFV) is a large DNA virus causing a highly contagious disease in domestic and wild boar, for which no treatment is available. ASFV vaccine development is hindered by large gaps in knowledge considering virus protein function and virus-host interaction. This study shows that the ASFV CP204L is a multifunctional protein engaged in endosomal trafficking and localizes to virus replication sites. Moreover, VPS39, a component of the HOPS complex, is a direct host interactor of CP204L. The virus CP204L binds the VPS39 domain responsible for its recruitment to the endosomal membrane, prevents its integration into the HOPS complex, and promotes the clustering of lysosomes. Additionally, we show that VPS39 is an important factor in the early phase of infection, as virus replication and protein synthesis in VPS39 knockout cells are delayed. These results uncover a novel function of viral protein CP204L and extend our understanding of complex interaction between virus and host, providing insights for developing a vaccine to prevent and control ASFV.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Sus Scrofa Domesticus (domestic Pig)

TISSUE(S): Epithelial Cell

SUBMITTER: Katarzyna Dolata

LAB HEAD: Axel Karger

PROVIDER: PXD035695 | Pride | 2023-01-23

REPOSITORIES: Pride

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