Defective viral genomes are highly abundant in natural H5N1 influenza infections

To successfully replicate inside infected cells, viruses must produce shared gene products, that can be used by multiple viral genomes within the same cell, and hence act as public goods. As a result, viral cheats can emerge, a type of molecular parasite formed by large deletions, which spread by exploiting public goods encoded by full-length viruses. Cheats exist across the viral universe, arise frequently in laboratory infections, and reflect the emergence of evolutionary conflict at the molecular level. If cheats are also common in natural viral infections, they could play a key role in viral population dynamics, pathogenesis, and adaptation. Here, we report the widespread abundance of viral cheats across diverse species infected by the recently emerged strain of H5N1 avian influenza. Within thousands of newly available deep-sequencing datasets, we use bioinformatic tools to find that the majority of infected animals contain viral cheats at detectable frequencies. Strikingly, in more than one in three animal infections, cheats reach a relative abundance greater than 50%, indicating that they are the majority variant within that population. We then interrogate this dataset using mathematical and statistical tools. Firstly, we show that viral cheats form distinct communities within each infected host, such that different host species are characterised by different viral cheat sequences becoming highly abundant. This indicates that an 'indicator species' approach to viral cheating could help identify the host species in viral sequences of unknown origin. Thirdly, we test for a genetic basis of susceptibility to cheating, finding that standing genetic variation exists for susceptibility to viral cheating within circulating H5N1 lineages. Overall, our findings suggest that: cheats are highly abundant in natural viral infections of diverse animal species.