The outcome of viral infection depends on the host's immune response, which must effectively defend against the pathogen. Viruses, in turn, evolve rapidly to overcome this response, particularly RNA viruses, whose high mutation rates facilitate cross-species transmission and viral emergence. This research examines how innate immune pathways shape viral evolution, by allowing two RNA viruses to adapt to Drosophila melanogaster with varying levels of antiviral immunity.
Inactivation of the RNA interference pathway resulted in higher genetic variation in viral populations. In addition, parallel fixation of mutations at a single capsid residue occurred independently of RNAi status, enhancing viral fitness. Manipulating the cGAS-STING pathway uncovered a recurrent mutation in a viral transmembrane protein. This mutation arose under normal or abolished, but not stimulated, immune signaling, implicating the protein in host adaptation. These findings indicate that the replication environment exerts stronger selective pressure than immune modulation alone and uncovered functional hotspots for viral adaptation.
Óscar Morales Lezcano (1995) studied Biochemistry at the University of Seville in 2017. He obtained an MSc diploma in Regenerative Biomedicine at the University of Granada in 2020. For his PhD, he joined the laboratory of Prof. Dr. Ronald van Rij at Radboud University Medical Center in Nijmegen, where he studied the effect of host innate immunity on RNA virus evolution.