Removing cellular transfer RNAs (tRNAs), making their cognate codons unreadable, creates a genetic firewall that prevents viral replication and horizontal gene transfer. However, numerous viruses and mobile genetic elements encode parts of the translational apparatus, including tRNAs, potentially rendering a genetic-code-based firewall ineffective. In this paper, we show that such horizontally transferred tRNA genes can enable viral replication in Escherichia coli cells despite the genome-wide lack of three codons and the previously essential cognate tRNAs and release factor 1. By repurposing viral tRNAs, we then develop recoded cells bearing an amino-acid-swapped genetic code that reassigns two of the six serine codons to leucine during translation. This amino-acid-swapped genetic code renders cells completely resistant to viral infections by mistranslating viral proteomes and prevents the escape of synthetic genetic information by engineered reliance on serine codons to produce leucine-requiring proteins. Finally, we also repurpose the third free codon to biocontain this virus-resistant host via dependence on an amino acid not found in nature.

中文翻译：

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交换的遗传密码阻止病毒感染和基因转移

去除细胞转移 RNA (tRNA)，使其同源密码子不可读，创建了阻止病毒复制和水平基因转移的遗传防火墙。然而，许多病毒和可移动的遗传元件对翻译装置的某些部分进行编码，包括 tRNA，这可能会使基于遗传密码的防火墙失效。在本文中，我们表明这种水平转移的 tRNA 基因可以使病毒在大肠杆菌中复制尽管全基因组缺乏三个密码子和以前必需的同源 tRNA 和释放因子 1。通过重新利用病毒 tRNA，我们开发了带有氨基酸交换遗传密码的重新编码细胞，将六个丝氨酸密码子中的两个重新分配给亮氨酸在翻译过程中。这种氨基酸交换的遗传密码通过错误翻译病毒蛋白质组使细胞完全抵抗病毒感染，并通过工程化依赖丝氨酸密码子产生需要亮氨酸的蛋白质来防止合成遗传信息的逃逸。最后，我们还通过对自然界中未发现的氨基酸的依赖，重新利用第三个自由密码子来生物控制这种抗病毒宿主。