The how of counter-defense: viral evolution to combat host immunity.

Viruses are locked in an evolutionary arms race with their hosts. What ultimately determines viral evolvability, or capacity for adaptive evolution, is their ability to efficiently explore and expand sequence space while under the selective regime imposed by their ecology, which includes innate and adaptive host defenses. Viral genomes have significantly higher evolutionary rates than their host counterparts and should have advantages relative to their slower-evolving hosts. However, functional constraints on virus evolutionary landscapes along with the modularity and mutational tolerance of host defense proteins may help offset the advantage conferred to viruses by high evolutionary rates. Additionally, cellular life forms from all domains of life possess many highly complex defense mechanisms that act as hurdles to viral replication. Consequently, viruses constantly probe sequence space through mutation and genetic exchange and are under pressure to optimize diverse counter-defense strategies.