Host obesity impacts genetic variation in influenza A viral populations.
Host obesity impacts genetic variation in influenza A viral populations.
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宿主肥胖会影响甲型流感病毒群体的遗传变异。
DOI：
10.1101/2023.07.12.548715
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Gresham,David
中科院分区：
文献类型：
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作者：
Knoll,Marissa;Honce,Rebekah;Meliopoulos,Victoria;Schultz-Cherry,Stacey;Ghedin,Elodie;Gresham,David
肥胖已被公认为许多非传染性疾病的风险因素;然而，人们对其对传染病的后果知之甚少。在这里，我们研究了宿主肥胖对甲型流感病毒（IAV）遗传变异的影响，使用饮食诱导的肥胖雪貂模型和A/Hong Kong/1073/1999（H9 N2）毒株。使用共笼研究设计，我们调查了维持，产生，并通过测序病毒基因组RNA从鼻洗样品在感染的多天内的宿主内IAV遗传变异的传输。我们发现的证据表明，在肥胖宿主中，正选择作用于新突变的作用增强，导致非同义变化上升到高频率。此外，我们发现了许多基因组突变的病例，这些突变是肥胖宿主特有的，并且在宿主之间的传播过程中被保留下来。尽管检测到肥胖特异性变体，但肥胖和瘦宿主之间的总体病毒遗传多样性没有显著差异。这可能是由于高供应率ofde novovariation和共同的进化适应的雪貂主机无论肥胖状态，我们表明是由血凝素和聚合酶基因（PB 2和PB 1）的变化介导的。我们还鉴定了在肥胖或瘦宿主中发现的独特缺陷病毒基因组（DVG），但两组之间的总体DVG多样性和动态没有差异。我们的研究表明，肥胖可能会导致一个独特的选择性环境，影响宿主内IAV的演变，强调需要额外的遗传和功能研究，以确认这些effects.IMPORTANCEObesity是一种慢性健康状况，其特征是过度肥胖导致炎症和代谢激素和免疫细胞群失调的全身性增加。甲型流感病毒（IAV）是引起季节性和大流行性流感的高度传染性病原体。宿主风险因素，包括免疫力低下和预先存在的健康状况，可能导致感染易感性增加和疾病严重程度增加。在病毒在宿主中复制期间，IAV的负义单链RNA基因组积累遗传多样性，这可能对病毒进化和传播产生重要影响。我们的研究首次深入了解了宿主肥胖对病毒遗传多样性和适应性的影响，表明与肥胖相关的宿主因素改变了病毒群体所经历的选择性环境，从而影响了遗传变异的谱。
Obesity is well established as a risk factor for many noncommunicable diseases; however, its consequences for infectious disease are poorly understood. Here, we investigated the impact of host obesity on influenza A virus (IAV) genetic variation using a diet-induced obesity ferret model and the A/Hong Kong/1073/1999 (H9N2) strain. Using a co-caging study design, we investigated the maintenance, generation, and transmission of intrahost IAV genetic variation by sequencing viral genomic RNA obtained from nasal wash samples over multiple days of infection. We found evidence for an enhanced role of positive selection acting onde novomutations in obese hosts that led to nonsynonymous changes that rose to high frequency. In addition, we identified numerous cases of mutations throughout the genome that were specific to obese hosts and that were preserved during transmission between hosts. Despite detection of obese-specific variants, the overall viral genetic diversity did not differ significantly between obese and lean hosts. This is likely due to the high supply rate ofde novovariation and common evolutionary adaptations to the ferret host regardless of obesity status, which we show are mediated by variation in the hemagglutinin and polymerase genes (PB2 and PB1). We also identified defective viral genomes (DVGs) that were found uniquely in either obese or lean hosts, but the overall DVG diversity and dynamics did not differ between the two groups. Our study suggests that obesity may result in a unique selective environment impacting intrahost IAV evolution, highlighting the need for additional genetic and functional studies to confirm these effects.IMPORTANCEObesity is a chronic health condition characterized by excess adiposity leading to a systemic increase in inflammation and dysregulation of metabolic hormones and immune cell populations. Influenza A virus (IAV) is a highly infectious pathogen responsible for seasonal and pandemic influenza. Host risk factors, including compromised immunity and pre-existing health conditions, can contribute to increased infection susceptibility and disease severity. During viral replication in a host, the negative-sense single-stranded RNA genome of IAV accumulates genetic diversity that may have important consequences for viral evolution and transmission. Our study provides the first insight into the consequences of host obesity on viral genetic diversity and adaptation, suggesting that host factors associated with obesity alter the selective environment experienced by a viral population, thereby impacting the spectrum of genetic variation.