期刊
ANNUAL REVIEW OF IMMUNOLOGY
卷 40, 期 -, 页码 271-294出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-immunol-072621-084422
关键词
evolutionary arms race; restriction factor; antibody; evolutionary landscape; deep mutational scan; mutation rates
类别
资金
- Hanna Gray fellowship
- HHMI
- Mathers Foundation
- NIH/NIAID [P50 AI150476]
Vertebrate immune systems use innate restriction factors and adaptive immunity to suppress viral infection. Viruses mutate to escape these defenses, driving hosts to counter-evolve. Viral proteins are subject to functional constraints. Evolutionary landscapes define the adaptive potential of all possible mutations. Deep mutational scanning experiments reveal the impact of landscapes on host and viral proteins engaged in arms races.
Vertebrate immune systems suppress viral infection using both innate restriction factors and adaptive immunity. Viruses mutate to escape these defenses, driving hosts to counterevolve to regain fitness. This cycle recurs repeatedly, resulting in an evolutionary arms race whose outcome depends on the pace and likelihood of adaptation by host and viral genes. Although viruses evolve faster than their vertebrate hosts, their proteins are subject to numerous functional constraints that impact the probability of adaptation. These constraints are globally defined by evolutionary landscapes, which describe the fitness and adaptive potential of all possible mutations. We review deep mutational scanning experiments mapping the evolutionary landscapes of both host and viral proteins engaged in arms races. For restriction factors and some broadly neutralizing antibodies, landscapes favor the host, which may help to level the evolutionary playing field against rapidly evolving viruses. We discuss the biophysical underpinnings of these landscapes and their therapeutic implications.
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