Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Curr Opin Virol. 2023 Jun;60:101326. doi: 10.1016/j.coviro.2023.101326. Epub 2023 Apr 7.
Following spillover, viruses must adapt to new selection pressures exerted by antiviral responses in their new hosts. In mammals, cellular defense mechanisms often include viral nucleic acid editing pathways mediated through protein families apolipoprotein-B mRNA-editing complex (APOBEC) and Adenosine Deaminase Acting on ribonucleic acid (ADAR). APOBECs induce C→U transitions in viral genomes; the APOBEC locus is highly polymorphic with variable numbers of APOBEC3 paralogs and target preferences in humans and other mammals. APOBEC3 paralogs have shaped the evolutionary history of human immunodeficiency virus, with compelling bioinformatic evidence also for its mutagenic impact on monkeypox virus and severe acute respiratory syndrome coronavirus 2. ADAR-1 induces adenose-to-inosine (A→I) substitutions in double-stranded ribonucleic acid (RNA); its role in virus adaptation is less clear, as are epigenetic modifications to viral genomes, such as methylation. Nucleic acid editing restricts evolutionary space in which viruses can explore and may restrict viral-host range.
病毒溢出后，必须适应新宿主抗病毒反应施加的新选择压力。在哺乳动物中，细胞防御机制通常包括通过载脂蛋白 B mRNA 编辑复合物 (APOBEC) 和腺苷脱氨酶作用于 RNA (ADAR) 蛋白家族介导的病毒核酸编辑途径。APOBEC 可诱导病毒基因组中的 C→U 转换；APOBEC 基因座在人类和其他哺乳动物中具有高度多态性，具有可变数量的 APOBEC3 基因家族和靶标偏好。APOBEC3 基因家族塑造了人类免疫缺陷病毒的进化史，有力的生物信息学证据也表明其对猴痘病毒和严重急性呼吸综合征冠状病毒 2 的诱变作用。ADAR-1 在双链核糖核酸 (RNA) 中诱导腺嘌呤到肌苷 (A→I) 取代；其在病毒适应中的作用尚不清楚，病毒基因组的表观遗传修饰，如甲基化，也是如此。核酸编辑限制了病毒可以探索的进化空间，并可能限制病毒的宿主范围。
