Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape.,Nature Communications

当前位置： X-MOL 学术 › Nat. Commun. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-17 , DOI: 10.1038/s41467-019-14174-2
Ahmed A Quadeer ₁ , John P Barton ₂ , Arup K Chakraborty _{3,

4,

5,

6,

7} , Matthew R McKay _{1,

8}

Affiliation

Vaccination has essentially eradicated poliovirus. Yet, its mutation rate is higher than that of viruses like HIV, for which no effective vaccine exists. To investigate this, we infer a fitness model for the poliovirus viral protein 1 (vp1), which successfully predicts in vitro fitness measurements. This is achieved by first developing a probabilistic model for the prevalence of vp1 sequences that enables us to isolate and remove data that are subject to strong vaccine-derived biases. The intrinsic fitness constraints derived for vp1, a capsid protein subject to antibody responses, are compared with those of analogous HIV proteins. We find that vp1 evolution is subject to tighter constraints, limiting its ability to evade vaccine-induced immune responses. Our analysis also indicates that circulating poliovirus strains in unimmunized populations serve as a reservoir that can seed outbreaks in spatio-temporally localized sub-optimally immunized populations.

中文翻译：

脊髓灰质炎病毒爆发的解卷积突变模式揭示了其固有的适应状况。

疫苗接种已根除脊髓灰质炎病毒。然而，它的突变率高于没有有效疫苗的像HIV这样的病毒。为了对此进行调查，我们推断出脊髓灰质炎病毒病毒蛋白1（vp1）的适应性模型，该模型成功地预测了体外适应性测量结果。这是通过首先为vp1序列的发生率开发一个概率模型来实现的，该模型使我们能够隔离和删除受疫苗强烈偏倚影响的数据。将vp1（一种经受抗体反应的衣壳蛋白）获得的固有适应性约束与类似HIV蛋白的固有适应性约束进行比较。我们发现vp1进化受到更严格的约束，限制了其规避疫苗诱导的免疫反应的能力。

更新日期：2020-01-17

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11