Arturo Diaz, PhD

Research Title:  The Role of Reticulons in the Formation and Function of Brome Mosaic Virus RNA Replication Compartments.

Project Summary: All positive-strand RNA viruses replicate their genomes in or on rearranged intracellular membranes, presenting opportunities for virus control (den Boon et al. (2010) Cell Host Microbe).  In this project, Dr. Arturo Diaz used the advanced bromovirus (BMV) RNA replication system to reveal varied mechanisms in viral membrane remodeling.  BMV RNA synthesis occurs in endoplasmic reticulum (ER) membrane invaginations induced by viral replication protein 1a, which has N-proximal RNA capping (1aN) and C-proximal helicase (1aC) domains. Dr. Arturo Diaz revealed that 1aN forms large hexagonal lattices in vivo, and implicated these interactions in membrane remodeling, supporting emerging results that 1a induces replication vesicles by forming a capsid-like interior shell (Diaz et al. (2012) J Virol).  Arturo also found that 1a induction of RNA replication vesicles requires host reticulons, a family of membrane-shaping proteins (Diaz et al. (2010) PNAS; Diaz and Ahlquist (2012) Curr Opin Microbiol).  He showed that 1a binds reticulons, relocalizes them to peri­nuclear ER sites of viral RNA replication, and incorporates them into viral RNA replication vesicles.  Arturo further contributed greatly to mapping 1a – membrane interaction to a 1aN amphipathic helix whose interaction with lipids served as a molecular switch controlling multiple 1a functions (Liu et al. (2009) PLoS Path), and to showing the dependence of replication vesicle formation on multiple lipid synthesis pathways (Wang et al. (2011), Zhang et al. (2012) J Virol).