Mapping the mutational landscape of an avian retrovirus envelope protein across its evolutionary trajectory

Many RNA viruses exhibit error-prone replication. Continuous generation of erroneous copies drives quasispecies dynamics and accelerates evolution. Avian leukosis virus subgroup J (ALV-J), an avian oncogenic virus, is a classic model virus for studying retroviruses. ALV-J's high mutation rates drive continuous evolution of its envelope and pathogenicity, posing significant challenges to the poultry industry. Here we employed deep mutational scanning to systematically assess envelope-wide mutation effects on ALV-J replication, integrating next-generation sequencing (NGS) with mutant libraries to identify critical envelope residues impacting viral fitness.