3D multi-target imaging of RNA virus replication deep in cells at the nanoscale

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The collaboration aims to lay the ground for the development and application of cutting-edge super-resolution imaging technology to study RNA virus-host interactions. This collaboration will have benefits for Canadians by directly contributing new imaging technology for new knowledge on the fundamental RNA virus biology and by indirectly contributing to the development of effective intervention strategies to battle RNA virus infection. The COVID-19 pandemic caused by an RNA virus, SARS-CoV-2, has resulted in over 40,000 deaths and an 18% GDP decline to date. RNA virus infection also causes livestock disease and economic loss. Canadian outbreaks of bovine spongiform encephalopathy cost $6.3 billion since the early 2000s and the 2004 outbreak of avian influenza in BC led to economic losses of up to $380 million. A positive RNA virus, norovirus, is a leading cause of foodborne diseases. To develop diagnostic and intervention strategies, we must understand the biological activity of the virus in its host. RNA virus relies on its host for survival and replication. Like other positive RNA viruses, norovirus (NoV) infection induces the remodeling of the host cell's intracellular membranes for the formation of viral replication complexes (RC, <300nm). NoV replication occurs in the RC, as well as virus assembly and export. The RC protects the viral genome from the host's innate immunity. The challenge is that the current technology does not allow direct visualization of the dynamics in the formation of the RC in the live specimen. The 2014 Nobel Prize-winning super-resolution imaging technology breaks the diffraction limit of light and allows the analysis of tiny RC structures and the detailed virus-host interactions on a single-molecule level in virus-infected live cells. This collaboration will foster the application of advanced bioimaging technology in studying the formation and structure of the NoV RC. The new knowledge on RNA virus replication and biogenesis uncovered by the new technology will inform the response plan for future outbreaks.