Evidence for a role of phenotypic mutations in virus adaptation Luzón Hidalgo, Raquel Risso, Valeria Alejandra Delgado Delgado, Asunción Andrés-León, Eduardo Ibarra Molero, Beatriz Sánchez Ruiz, José Manuel This work was supported by Spanish Ministry of Economy and Competitiveness/FEDER Funds Grant RTI2018-097142-B-100 and by Human Frontier Science Program Grant RGP0041/2017. Viral genome library preparation and Illumina sequencing were carried out at the IPBLN Genomics Facility (CSIC, Granada, Spain), and the assistance of Dr. Alicia Barroso del Jesus is gratefully acknowledged. We also thank Dr. Jon Beckwith and Dr. Dana Boyd (Harvard University) for kindly providing knockout strains used in this work. Supplemental information can be found online at https://doi.org/10.1016/j.isci.2021.102257. Viruses interact extensively with the host molecular machinery, but the underlying mechanisms are poorly understood. Bacteriophage T7 recruits the small protein thioredoxin of the Escherichia coli host as an essential processivity factor for the viral DNA polymerase. We challenged the phage to propagate in a host in which thioredoxin had been extensively modified to hamper its recruitment. The virus adapted to the engineered host without losing the capability to propagate in the original host, but no genetic mutations were fixed in the thioredoxin binding domain of the viral DNA polymerase. Virus adaptation correlated with mutations in the viral RNA polymerase, supporting that promiscuous thioredoxin recruitmentwas enabled by phenotypicmutations caused by transcription errors. These results point to a mechanism of virus adaptation that may play a role in cross-species transmission.We propose that phenotypicmutations may generally contribute to the capability of viruses to evade antiviral strategies 2021-05-05T12:31:13Z 2021-05-05T12:31:13Z 2021-04-23 info:eu-repo/semantics/article Luzon-Hidalgo et al. Evidence for a role of phenotypic mutations in virus adaptation. iScience 24, 102257 [https://doi.org/10.1016/j.isci.2021.102257] http://hdl.handle.net/10481/68346 10.1016/j.isci.2021.102257 eng http://creativecommons.org/licenses/by-nc-nd/3.0/es/ info:eu-repo/semantics/openAccess Atribución-NoComercial-SinDerivadas 3.0 España Elsevier