Spin models inferred from patient-derived viral sequence data faithfully describe HIV fitness landscapes

摘要

Mutational escape from vaccine-induced immune responses has thwarted the development of a successfulnvaccine against AIDS, whose causative agent is HIV, a highly mutable virus. Knowing the virus’ fitness as anfunction of its proteomic sequence can enable rational design of potent vaccines, as this information can focusnvaccine-induced immune responses to target mutational vulnerabilities of the virus. Spin models have beennproposed as a means to infer intrinsic fitness landscapes of HIV proteins from patient-derived viral proteinnsequences. These sequences are the product of nonequilibrium viral evolution driven by patient-specific immunenresponses and are subject to phylogenetic constraints. How can such sequence data allow inference of intrinsicnfitness landscapes? We combined computer simulations and variational theory ´a la Feynman to show that, innmost circumstances, spin models inferred from patient-derived viral sequences reflect the correct rank order ofnthe fitness of mutant viral strains. Our findings are relevant for diverse viruses.