Picornaviruses are small, positive-sense single-stranded RNA viruses including many important human pathogens as well as infecting a wide range of other mammals such as livestock. Within the host cell, these viruses replicate at specific replication sites called replication organelles. In order to remodel the host membranes and to create the replication organelles, these viruses hijack several host factors including the lipid kinase phosphatidyl-inositol 4-kinase beta (PI4KB, [1]) and the acyl-CoA-binding domain-containing protein-3 (ACBD3, [2]). Using X-ray crystallography, we solved the structures of the protein complexes formed by the non-structural 3A proteins from several picornavirus species and the appropriate interacting domain of ACBD3. We show that the viral 3A proteins act as molecular harnesses to enslave the ACBD3 protein leading to its stabilization at target membranes, which leads in turn to the recruitment and activation of the PI4KB kinase. Our structural analysis explains how these viral-host protein complexes assemble at the membrane and identifies new potential targets for antiviral therapies.
The work was supported by the Czech Science Foundation (grant number 17-07058Y), Academy of Sciences of the Czech Republic (RVO: 61388963), and Ministry of Education, Youth and Sports of the Czech Republic (project InterBioMed - LO1302).
Figure 1