Genetic drift and purifying selection shape within-host influenza A virus populations during natural swine infections.
Genetic drift and purifying selection shape within-host influenza A virus populations during natural swine infections.
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在自然猪感染期间，遗传漂变和纯化选择塑造了宿主甲型流感病毒种群。
DOI：
10.1101/2023.10.23.563581
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Koelle,Katia
中科院分区：
文献类型：
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作者：
VanInsberghe,David;McBride,DillonS;DaSilva,Juliana;Stark,ThomasJ;Lau,MaxSY;Shepard,SamuelS;Barnes,JohnR;Bowman,AndrewS;Lowen,AniceC;Koelle,Katia
宿主内甲型流感病毒（IAV）的多样性和进化模式已在自然人类感染中得到描述，但这些模式在非人类宿主中的特征仍然很差。阐明这些动力学对于更好地理解IAV生物学和控制人类溢出的进化过程非常重要。在这里，我们在为期一周的县博览会期间对猪中的IAV爆发进行了采样，以表征这一重要储库宿主中的病毒多样性和进化。每天从展会上的所有猪身上采集鼻拭子，每天最多可采集421份样本。PCR阳性标本的分型结果显示H1N1和H3N2亚型猪IAV存在共循环。对具有稳健Ct值的PCR阳性样品进行深度测序，从总共253头猪中产生506个测序样品。基于来自这些最初测序的样本的子集（来自168头猪的260个样本）的更高深度的重新测序数据，我们表征了宿主内IAV遗传多样性和进化的模式。我们发现单亚型感染猪的IAV遗传多样性较低，大多数宿主内单核苷酸变异体（iSNV）的频率<10%。非同义iSNV的数量与同义iSNV的数量之比显著低于中性预期，表明纯化选择塑造了猪体内宿主内病毒多样性的模式。iSNV的动态更新及其显著的频率变化进一步表明，遗传漂变在猪体内形成IAV群体中也起着重要作用。总之，我们的研究结果突出了人类和猪之间IAV遗传多样性和进化模式的相似性，包括随机过程在塑造宿主内IAV动态中的作用。
Patterns of within-host influenza A virus (IAV) diversity and evolution have been described in natural human infections, but these patterns remain poorly characterized in non-human hosts. Elucidating these dynamics is important to better understand IAV biology and the evolutionary processes that govern spillover into humans. Here, we sampled an IAV outbreak in pigs during a week-long county fair to characterize viral diversity and evolution in this important reservoir host. Nasal wipes were collected on a daily basis from all pigs present at the fair, yielding up to 421 samples per day. Subtyping of PCR-positive samples revealed the co-circulation of H1N1 and H3N2 subtype swine IAVs. PCR-positive samples with robust Ct values were deep-sequenced, yielding 506 sequenced samples from a total of 253 pigs. Based on higher-depth re-sequenced data from a subset of these initially sequenced samples (260 samples from 168 pigs), we characterized patterns of within-host IAV genetic diversity and evolution. We find that IAV genetic diversity in single-subtype infected pigs is low, with the majority of intrahost Single Nucleotide Variants (iSNVs) present at frequencies of <10%. The ratio of the number of nonsynonymous to the number of synonymous iSNVs is significantly lower than under the neutral expectation, indicating that purifying selection shapes patterns of within-host viral diversity in swine. The dynamic turnover of iSNVs and their pronounced frequency changes further indicate that genetic drift also plays an important role in shaping IAV populations within pigs. Taken together, our results highlight similarities in patterns of IAV genetic diversity and evolution between humans and swine, including the role of stochastic processes in shaping within-host IAV dynamics.