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

<!-- /* Font Definitions */@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:"MS ??";panose-1:0 0 0 0 0 0 0 0 0 0;mso-font-alt:"ＭＳ 明朝";mso-font-charset:128;mso-generic-font-family:auto;mso-font-format:other;mso-font-pitch:variable;mso-font-signature:0 134676480 16 0 131072 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Times New Roman";mso-fareast-font-family:"MS ??";mso-bidi-font-family:"Times New Roman";mso-ansi-language:EN-GB;mso-fareast-language:JA;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:11.0pt;mso-ansi-font-size:11.0pt;mso-bidi-font-size:11.0pt;mso-fareast-font-family:"MS ??";mso-ansi-language:ES-TRAD;mso-fareast-language:JA;}@page WordSection1{size:612.0pt 792.0pt;margin:70.85pt 3.0cm 70.85pt 3.0cm;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->Infectious BursalDisease Virus (IBDV), the best-characterized memberof the Birnaviridae family, is theaetiological agent of Gumboro disease, causing enormous economic losses to thepoultry industry globally. In contrast to prototypical dsRNA (members of the Reoviridae family), and similar to thereplicative complex of single stranded RNA viruses, Birnaviruses lack a ?transcriptionalcore?, instead their genomes are packaged in filamentous structures calledribonucleoproteins (RNPs). Indeed, this key structural/functional disparitysuggests that Birnaviruses use an as yet poorly characterized unique replicationstrategy encouraging us to make a great effort in understanding theirreplication mechanism and its interactions with host cell elements. We have analysedthe IBDV internalization process and the post-internalization traffic, showingthat viral particles exploit the macropinocytic pathway and traffic through theendocytic pathway in a Rab5-dependent manner. Furthermore, we demonstrated thatthe RNPs, built by the dsRNA genome segments, the RNA-dependent RNA polymerase(RdRP, VP1) and VP3 (a dsRNA-binding protein), are located in endosomalstructures associated to the Golgi complex. We further observed that VP3 actsas a flagstone element associating with biologically relevant lipids present atthe cytosolic face of endosomes, to orchestrate the replication machinery fromwhich the virus depends for its successful infection cycle.