Another hijack! Some enteroviruses co-opt the c10orf76/PI4KB complex for their own good

Abstract

Enteroviruses, members of the Picornaviridae family, are non-enveloped and single-stranded RNA viruses responsible for several human diseases. During infection, these viruses build membrane-bound organelles, called replication organelles (ROs), where new virions are assembled. ROs are highly enriched in phosphatidylinositol 4-phosphate (PI4P) produced by the host lipid kinase PI4KB. In this issue of EMBO Reports, McPhail et al [1] characterize a complex, formed by PI4KB and the c10orf76 protein, which is involved in PI4P production. They show that this machinery is hijacked by specific enteroviruses such as coxsackievirus A10 for their replication.

Figure 1. c10orf76 links PI4P metabolism and viral replication

In coxsackievirus A10‐infected cells, while the Golgi collapses, PI4P is highly enriched at the limiting membrane of specific organelles named replication organelles (ROs). In uninfected cells, the Golgi localization of PI4KB is controlled by its Golgi‐localized protein partner ACBD3. c10orf76 directly interacts with PI4KB at the Golgi membrane and regulates the recruitment of GBF1 (arrow 1), a GEF and activator of the small GTPase Arf1. In its GTP‐bound form, Arf1 activates PI4KB (arrow 2). In coxsackievirus A10‐infected cells, this c10orf76/PI4KB‐dependent PI4P synthesis machinery is hijacked at the surface of ROs. This hijacking is controlled by the RO‐localized viral protein 3A, which mediates the recruitment of GBF1 and ACDB3, which in turn drives the recruitment of Arf1 and PI4KB.