Pseudorabies virus hijacks Rab6 protein to promote viral assembly

Abstract Pseudorabies virus (PRV) is the causative agent of Aujeszky's disease, also known as pseudorabies, in pigs. Rab6, a small GTPase, is thought to be essential for certain membrane trafficking activities and is associated with the regulation of exocytosis. Whether Rab6 is involved in PRV infection has not been previously reported. We found that the mRNA and protein levels of Rab6 were significantly upregulated in PK-15 cells and porcine alveolar macrophages, as well as in the lungs and spleen of PRV-infected mice. Overexpression of the wild-type and GTP-bound mutant of Rab6 promoted PRV proliferation, while the GDP-bound mutant inhibited it, suggesting that the GTPase activity of Rab6 is critical for PRV propagation. We further confirmed that knockdown of Rab6 inhibited PRV proliferation. Additionally, our results demonstrated that Rab6 knockdown disrupted PRV assembly. Mechanistically, Rab6 interacted with PRV glycoproteins gB and gE, which are crucial for PRV assembly. Our data suggest that PRV co-opts Rab6 to facilitate viral assembly and provide a potential new therapeutic target for PRV infection.