The ribosomal landscape in influenza A virus infection: from molecular mechanisms to clinical relevance

Influenza A virus (IAV) infections continue to represent a significant global health concern, both in terms of severe individual cases of acute respiratory distress syndrome (ARDS) and the potential for the emergence of pandemics. Despite decades of research, therapeutic options remain limited and the pathogenesis of severe disease is not yet fully understood. One critical yet underappreciated aspect is how IAV reprogrammes the ribosomal landscape of the host to facilitate viral replication and evade immune responses. Ribosomes take centre stage during infection, as both the immune response and viral propagation depend on the protein synthesis machinery. Recent studies have shown that the ribosome is not a static structure but can undergo dynamic changes in composition and function (ribosomal heterogeneity), which may influence the balance between viral propagation and host defence. Additionally, cancer research has remarkably demonstrated the feasibility of targeting the ribosome therapeutically. In this review, we summarise emerging evidence on how IAV hijacks the ribosomal landscape, including ribosomal biogenesis, ribosomal proteins, translation factors and associated signalling pathways, and how these changes may shape the course of infection, immune response and lung injury. Drawing parallels with cancer biology, we explore whether components of this reprogrammed landscape could serve as therapeutic targets in severe IAV infection and ARDS. By connecting molecular mechanisms with clinical relevance, we aim to highlight a novel perspective on host-virus interaction that could open avenues for future treatment strategies.

• Pott, J.
• Kryvenko, V.
• Vadász, I.