Sobel Leonard Ashley, Mendoza Lydia, McFarland Alexander G, Marques Andrew D, Everett John K, Moncla Louise, Bushman Frederic D, Odom John Audrey R, Hensley Scott E
Division of Infectious Diseases, Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA.
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd., Philadelphia, PA 19104, USA.
Virus Evol. 2024 Apr 25;10(1):veae034. doi: 10.1093/ve/veae034. eCollection 2024.
Seasonal influenza virus predominantly evolves through antigenic drift, marked by the accumulation of mutations at antigenic sites. Because of antigenic drift, influenza vaccines are frequently updated, though their efficacy may still be limited due to strain mismatches. Despite the high levels of viral diversity observed across populations, most human studies reveal limited intrahost diversity, leaving the origin of population-level viral diversity unclear. Previous studies show host characteristics, such as immunity, might affect within-host viral evolution. Here we investigate influenza A viral diversity in children aged between 6 months and 18 years. Influenza virus evolution in children is less well characterized than in adults, yet may be associated with higher levels of viral diversity given the lower level of pre-existing immunity and longer durations of infection in children. We obtained influenza isolates from banked influenza A-positive nasopharyngeal swabs collected at the Children's Hospital of Philadelphia during the 2017-18 influenza season. Using next-generation sequencing, we evaluated the population of influenza viruses present in each sample. We characterized within-host viral diversity using the number and frequency of intrahost single-nucleotide variants (iSNVs) detected in each sample. We related viral diversity to clinical metadata, including subjects' age, vaccination status, and comorbid conditions, as well as sample metadata such as virus strain and cycle threshold. Consistent with previous studies, most samples contained low levels of diversity with no clear association between the subjects' age, vaccine status, or health status. Further, there was no enrichment of iSNVs near known antigenic sites. Taken together, these findings are consistent with previous observations that the majority of intrahost influenza virus infection is characterized by low viral diversity without evidence of diversifying selection.
季节性流感病毒主要通过抗原漂移进化，其特征是抗原位点处的突变积累。由于抗原漂移，流感疫苗经常更新，不过由于毒株不匹配，其效力可能仍然有限。尽管在不同人群中观察到高水平的病毒多样性，但大多数人体研究显示宿主内多样性有限，群体水平病毒多样性的起源尚不清楚。先前的研究表明，宿主特征（如免疫力）可能会影响宿主内病毒的进化。在此，我们调查了6个月至18岁儿童的甲型流感病毒多样性。儿童流感病毒的进化特征不如成人明确，但鉴于儿童预先存在的免疫力水平较低且感染持续时间较长，可能与更高水平的病毒多样性有关。我们从费城儿童医院在2017 - 18流感季节收集的储存甲型流感阳性鼻咽拭子中获得流感分离株。使用下一代测序技术，我们评估了每个样本中存在的流感病毒群体。我们使用在每个样本中检测到的宿主内单核苷酸变异（iSNV）的数量和频率来表征宿主内病毒多样性。我们将病毒多样性与临床元数据相关联，包括受试者的年龄、疫苗接种状况和合并症，以及样本元数据，如病毒株和循环阈值。与先前的研究一致，大多数样本的多样性水平较低，受试者的年龄、疫苗接种状况或健康状况之间没有明显关联。此外，在已知抗原位点附近没有iSNV的富集。综上所述，这些发现与先前的观察结果一致，即大多数宿主内流感病毒感染的特征是病毒多样性低，且没有多样化选择的证据。
