Matryoshka Dolls of Virus Evolution: the Internal Forces That Shape Viral Fate.

Abstract

Viral evolution unfolds across nested layers of adaptation, much like a set of Matryoshka dolls. The outermost, well-studied layer involves interactions between viruses and their hosts-where immune evasion, cross-species transmission, and long-term coevolution drive viral diversification. Yet, hidden within this framework is an often-overlooked inner layer: the coevolution of viruses with their own molecular parasites, defective interfering (DI) particles and defective viral genomes (DVGs). These molecular parasites exploit viral replication machinery, reshaping infection dynamics and imposing selective pressures that influence viral fitness, transmission, and persistence. This perspective synthesizes evidence from experimental evolution, mathematical modeling, and molecular virology to propose a more integrated view of viral evolution. By framing host-virus interactions and virus-DI particle dynamics within a unified evolutionary framework, we highlight the underappreciated role of DI particles as evolutionary players, not just aberrant byproducts. Recognizing these internal layers of viral evolution may inform the development of antiviral strategies and broader questions in host-pathogen coevolution.