Biogenesis of viral factories

Infectious diseases continue to be the main cause of death worldwide. In particular, RNA viruses are devastating pathogens for humans, animals and plants. We are studying the replication factories assembled by several RNA viruses which are important human pathogens such as Bunyaviruses, Reoviruses and Infuenza viruses.

RNA viruses replicate their genomes on intracelIular membranes. Viruses recruit cell organelles and numerous viral and cellular factors to build their replication platforms also known as “viral factories”. Due to the complex interactions detected in these structures, viral factories could be considered as the actual living state of viruses. In the CSL we are searching for the key factors involved in the biogenesis of viral factories to understand how viruses manipulate cell organization and build new organelles. Our goal is to identify the structures that support virus replication, morphogenesis and egress to unveil potential targets for new antivirals.

We noticed that most RNA viral factories share two common characteristics: (1) new synthesis and rearrangement of membranes, and (2) mitochondrial  recruitmet around replication complexes. Rearrangemet of membranes to build replication organelles also requires a specific lipid composition. Viruses interfere with cellular lipid flows during infection, taking advantage of specific lipid transfer proteins (LTPs). On the other hand, mitochondrial network suffers severe morphological changes during infection. We are characterizing the LTPs usurped proteins LTP usurped by bunyaviruses and the structural and functional changes of the mitochondrial network after bunyavirus infection, and which viral and cellular factors are involved.

Fernández de Castro, Tenorio & Risco., Current Opinion in Virology 2016; Fernández de Castro et al., mBio 2014; Risco et al., Annual Review of Virology, 2014; Fernández de Castro & Risco, Future Virology 2014. Tenorio et al., mBio 2018; Sachse et al., Advances in Virus Reseach 2019: Tenorio et al., Viruses 2019.

MinecoNihcamCNBCSICSevero Ochoa