Viral Genetic Determinants of Prolonged Respiratory Syncytial Virus Infection Among Infants in a Healthy Term Birth Cohort.
Viral Genetic Determinants of Prolonged Respiratory Syncytial Virus Infection Among Infants in a Healthy Term Birth Cohort.
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DOI：
10.1093/infdis/jiac442
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发表时间：
2023-05-12
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影响因子：
--
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呼吸道合胞病毒（RSV）与急性呼吸道感染有关。我们试图鉴定与长期感染相关的RSV变体。在健康足月婴儿中，我们确定了那些长期RSV感染的婴儿，并进行了（1）人类全基因组关联研究（GWAS）以测试感染风险对宿主基因型的依赖性，（2）使用RSV全基因组测序进行病毒GWAS与长期RSV感染的关联性，（3）分析所有病毒公共序列，（4）评估免疫应答，以及（5）所有主要功能数据的汇总。对病毒/人群结构和与感染风险相关的宿主因素进行了调整。我们在G蛋白中鉴定了与长期感染相关的p.E123K/D和p.P218T/S/L（Padj = .01）。我们没有发现宿主遗传感染风险的证据。RSV变异体的位置与可能结合假定的病毒受体硫酸乙酰肝素的序列接近。通过对病毒和宿主遗传学的分析，我们发现了一种与其他健康婴儿长期感染相关的新型RSV变体，没有证据支持宿主对感染的遗传易感性。由于RSV的慢性能力及其病毒库尚未确定，因此这些发现对于了解RSV对慢性疾病和地方病的影响非常重要。对宿主和病毒遗传学的综合计算统计分析为RSV病毒在健康人类婴儿中的持久性提供了令人信服的证据，这一发现对于了解RSV对慢性疾病和病毒流行的影响具有重要意义。
Respiratory syncytial virus (RSV) is associated with acute respiratory infection. We sought to identify RSV variants associated with prolonged infection. Among healthy term infants we identified those with prolonged RSV infection and conducted (1) a human genome-wide association study (GWAS) to test the dependence of infection risk on host genotype, (2) a viral GWAS for association with prolonged RSV infection using RSV whole-genome sequencing, (3) an analysis of all viral public sequences, (4) an assessment of immunological responses, and (5) a summary of all major functional data. Analyses were adjusted for viral/human population structure and host factors associated with infection risk. We identified p.E123K/D and p.P218T/S/L in G protein that were associated with prolonged infection (Padj = .01). We found no evidence of host genetic risk for infection. The RSV variant positions approximate sequences that could bind a putative viral receptor, heparan sulfate. Using analysis of both viral and host genetics we identified a novel RSV variant associated with prolonged infection in otherwise healthy infants and no evidence supporting host genetic susceptibility to infection. As the capacity of RSV for chronicity and its viral reservoir are not defined, these findings are important for understanding the impact of RSV on chronic disease and endemicity. A comprehensive computational statistical analysis of both host and viral genetics provided compelling evidence for RSV viral persistence in healthy human infants, a finding of significant importance to understanding the impact of RSV on chronic disease and viral endemicity.
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影响因子：
3.7
作者：
Bokun, Vladimir;Moore, John J.;Piedimonte, Giovanni
通讯作者：
Piedimonte, Giovanni
影响因子：
3.7
作者：
Eshaghi A;Duvvuri VR;Lai R;Nadarajah JT;Li A;Patel SN;Low DE;Gubbay JB
通讯作者：
Gubbay JB
DOI：
10.1056/nejmoa0804877
发表时间：
2009-02-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hall CB;Weinberg GA;Iwane MK;Blumkin AK;Edwards KM;Staat MA;Auinger P;Griffin MR;Poehling KA;Erdman D;Grijalva CG;Zhu Y;Szilagyi P
通讯作者：
Szilagyi P
影响因子：
5.1
作者：
O'Donnell, DR;McGarvey, MJ;Openshaw, PJM
通讯作者：
Openshaw, PJM
影响因子：
3.7
作者：
Okiro, Emelda A.;White, Lisa J.;Nokes, D. James
通讯作者：
Nokes, D. James