Cell Biology of Viral Infection

Influenza A virus is a major human pathogen that causes yearly epidemics and occasional pandemic outbreaks. Despite a tight surveillance and a yearly vaccination scheme, the pathogen is responsible for high mortality, morbidity and economic damage. Development of antivirals is therefore necessary. The elucidation of cellular pathways used by the virus, can contribute to identify novel therapeutic targets. The virus genome consists of 8 segments of negative sense, single stranded RNA (vRNAs) that encodes 10-12 identified proteins. Each vRNA is separately encapsidated into ribonucleoprotein (RNP) particles by the trimeric viral RNA polymerase (PB1, PB2 and PA) and RNA-binding protein NP. Unusually for an RNA virus, the genome is transcribed and replicated in the host cell nucleus. After exiting this compartment, new vRNPs reach the apical side of the PM using at least a two-step mechanism in the cytoplasm: first they accumulate around the microtubule organizing centre where they are loaded onto Rab11-vesicles and are then transported using both microtubules and actin to the cell periphery. Understanding the mechanisms that govern vesicular trafficking (and therapeutic methods to inhibit them) is the main focus the research plan of the lab. The factors involved in the biogenesis of vesicles carrying viral genome, or in the anchoring and fusion to target membranes will be investigated, as well as molecular motors involved in this transport. As the virion is composed not only of vRNPs but also 5 other viral proteins, the cellular pathways involved in their trafficking to the budzone will be addressed. Ultimately we are interested in understanding the process of viral assembly and budding from the cells.