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表型突变在病毒适应性中作用的证据。

Evidence for a role of phenotypic mutations in virus adaptation.

作者信息

Luzon-Hidalgo Raquel, Risso Valeria A, Delgado Asuncion, Andrés-León Eduardo, Ibarra-Molero Beatriz, Sanchez-Ruiz Jose M

机构信息

Departamento de Quimica Fisica. Facultad de Ciencias, Unidad de Excelencia de Quimica Aplicada a Biomedicina y Medioambiente (UEQ), Universidad de Granada, Granada 18071, Spain.

Unidad de Bioinformática. Instituto de Parasitología y Biomedicina "López Neyra", CSIC, Armilla, Granada 18016, Spain.

出版信息

iScience. 2021 Mar 2;24(4):102257. doi: 10.1016/j.isci.2021.102257. eCollection 2021 Apr 23.

DOI:10.1016/j.isci.2021.102257
PMID:33817569
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8010470/
Abstract

Viruses interact extensively with the host molecular machinery, but the underlying mechanisms are poorly understood. Bacteriophage T7 recruits the small protein thioredoxin of the 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 recruitment was enabled by phenotypic mutations 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 phenotypic mutations may generally contribute to the capability of viruses to evade antiviral strategies.

摘要

病毒与宿主分子机制广泛相互作用，但其潜在机制仍知之甚少。噬菌体T7招募宿主的小蛋白硫氧还蛋白作为病毒DNA聚合酶的重要持续性因子。我们让噬菌体在硫氧还蛋白经过广泛修饰以阻碍其招募的宿主中增殖。该病毒适应了工程改造的宿主，同时又不丧失在原始宿主中增殖的能力，但病毒DNA聚合酶的硫氧还蛋白结合结构域未发生固定的基因突变。病毒适应与病毒RNA聚合酶中的突变相关，这支持了转录错误导致的表型突变使得硫氧还蛋白的杂乱招募成为可能。这些结果指向一种病毒适应机制，该机制可能在跨物种传播中发挥作用。我们提出，表型突变可能普遍有助于病毒逃避抗病毒策略的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/4d68e2c57d06/gr11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/1a8e8be9118f/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/fdd1988d2252/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/bd7f87f5df96/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/b562add4f323/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/35ed0047854c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/a17f595edaf3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/ca1039745cf1/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/a9ec8f5c809a/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/44c4774a59cb/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/98c8ddb3fe79/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/ff36893196e2/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/4d68e2c57d06/gr11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/1a8e8be9118f/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/fdd1988d2252/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/bd7f87f5df96/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/b562add4f323/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/35ed0047854c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/a17f595edaf3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/ca1039745cf1/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/a9ec8f5c809a/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/44c4774a59cb/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/98c8ddb3fe79/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/ff36893196e2/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bcf/8010470/4d68e2c57d06/gr11.jpg

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本文引用的文献

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Applying next-generation sequencing to unravel the mutational landscape in viral quasispecies.应用下一代测序技术揭示病毒准种中的突变景观。
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Non-conservation of folding rates in the thioredoxin family reveals degradation of ancestral unassisted-folding.硫氧还蛋白家族中折叠速率的非守恒性揭示了祖先无辅助折叠的降解。
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Destabilizing mutations encode nongenetic variation that drives evolutionary innovation.不稳定突变编码了驱动进化创新的非遗传变异。
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Host Factors in Coronavirus Replication.冠状病毒复制中的宿主因素。
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Using Resurrected Ancestral Proviral Proteins to Engineer Virus Resistance.利用复活的祖传前病毒蛋白构建病毒抗性
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Conserved rates and patterns of transcription errors across bacterial growth states and lifestyles.细菌不同生长状态和生活方式下转录错误的保守速率和模式。
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