AntiViralStress – Investigating the synergetic role of ER stress in mounting an antiviral response

Cellular response to Endoplasmic Reticulum (ER) stress plays a role in virus infection in more than one way. Preliminary data point to the role of the ER stress response induced by flavivirus infection in priming the innate antiviral activity in infected cells.

The synergy between ER stress and Pattern Recognition Receptors (PRR) in augmenting the interferon (IFNβ) response is an intriguing new vision of the early events following viral infection, where ER stress acts as a cellular “danger sensor” that can alert the cell and prime the innate response to react to the pathogen. With the help of a deeper investigation, this may lead to the development of new therapeutic approaches.

OBJECTIVES

• Investigate the causal link between the innate antiviral response and ER stress induction following infection with flaviviruses.
• Investigate the chain of events that, from ER stress, leads to IFNβ production through the phosphorylation of IRF3.
• Investigate how different flaviviruses may lead to the same outcome, cellular innate response, by activating different ER stress pathways.
• Explore the contribution of ER stress during virus infection.
• Verify to what extent ER stress-PRR synergy is specific to flaviviruses or may be extended to other viruses, like coronaviruses.