Endosomal membranes as the platform for Infectious Bursal Disease Virus replication inside the cell: the protagonist role of the moonlighting VP3 protein

DELGUI, LAURA R.

Londres

Congreso; Focused Meeting 2016 ? Molecular Biology and Pathogenesis of Avian Viruses; 2016

Microbiology Society

Infectious Bursal Disease Virus (IBDV), the best-characterized member of the Birnaviridae family, is the aetiological agent of Gumboro disease, causing enormous economic losses to the poultry industry globally. In contrast to prototypical dsRNA (members of the Reoviridae family), and similar to the replicative complex of single stranded RNA viruses, Birnaviruses lack a “transcriptional core”, instead their genomes are packaged in filamentous structures called ribonucleoproteins (RNPs). Indeed, this key structural/functional disparity suggests that Birnaviruses use an as yet poorly characterized unique replication strategy encouraging us to make a great effort in understanding their replication mechanism and its interactions with host cell elements. We have analysed the IBDV internalization process and the post-internalization traffic, showing that viral particles exploit the macropinocytic pathway and traffic through the endocytic pathway in a Rab5-dependent manner. Furthermore, we demonstrated that the RNPs, built by the dsRNA genome segments, the RNA-dependent RNA polymerase (RdRP, VP1) and VP3 (a dsRNA-binding protein), are located in endosomal structures associated to the Golgi complex. We further observed that VP3 acts as a flagstone element associating with biologically relevant lipids present at the cytosolic face of endosomes, to orchestrate the replication machinery from which the virus depends for its successful infection cycle.