Mechanogenomic regulation of host-pathogen (Coronavirus) interactions and its interplay with cellular ageing
Most human coronaviruses cause mild to moderate upper-respiratory tract illness (although lower respiratory tract infections can also occur) in young children, elderly and immunocompromised individuals. These viruses (such as COVID-19) are highly infective with considerable fatality rate (in particular in high-risk groups including the elderly and those with underlying chronic medical conditions). Thus, better understanding of coronavirus virulence mechanisms is emerging as a pressing matter. Recent work has shown that coronaviruses use the NF-κB pathway for their replication and propagation. Interestingly, our prior work had revealed that the NF-κB signalling pathway is tightly linked to tissue mechanics. Since tissue stiffness increases with aging, we hypothesize that the interplay between cell mechanics and the activation of NF-κB pathway during coronavirus infection could explain the high replication and propagation of coronaviruses in the ageing population. In future work, we will study the functional links between viral replication, cytoskeletal-dependent signalling and 3D genome organization in host cells using an in-vitro lung epithelial cell model mimicking young and old tissue rigidities with and without coronavirus infection.