Virus Replication: The Role of the Unique Pathogenic Organelle

Recent years have seen an explosion in our knowledge on the molecular interplay between viruses and their hosts. Plus-stranded RNA viruses, such as Sars-CoV-2 or Dengue virus, recruit cellular vesicles and co-opt cellular proteins involved in metabolism and lipid biosynthesis to build viral replicase complexes within the large viral replication organelles. We use tombusviruses (TBSV), which are small (+)RNA viruses, as model plant viruses to study virus replication, recombination, and virus - host interactions using yeast (Saccharomyces cerevisiae) surrogate host. Several systematic genome-wide screens and global proteomics and lipidomics approaches have led to the identification of ~500 host proteins/genes that are implicated in TBSV replication. We characterized the role of ~100 co-opted host proteins, sterols and phospholipids in tombusvirus replication organelle biogenesis. We will present an integrated view how tombusviruses built the replication organelle through co-opting cellular proteins and subverting cellular pathways. Finally, we show evidence that TBSV uses the replication organelle to protect the viral RNA in a unique microenvironment from degradation by the host antiviral machinery. Altogether, hijacking of cellular proteins and networks is key for TBSV to exert supremacy over the host cell leading to robust replication of the viral RNA. 

 
Learning Objectives:

1. Virus-host interaction network

2. Understanding viral replication

3. Broad-spectrum antiviral approaches