Al Khatib Hebah A, Al Maslamani Muna A, Coyle Peter V, Thompson I Richard, Farag Elmoubasher A, Al Thani Asmaa A, Yassine Hadi M
Life Science Division, College of Science and Engineering, Hamad Ben Khalifah University, Doha 34110; Qatar.
Communicable Diseases Center, Hamad Medical Corporation, Doha 3050, Qatar.
Microorganisms. 2020 Jan 17;8(1):133. doi: 10.3390/microorganisms8010133.
The diversity of RNA viruses dictates their evolution in a particular host, community or environment. Here, we reported within- and between-host pH1N1virus diversity at consensus and sub-consensus levels over a three-year period (2015-2017) and its implications on disease severity. A total of 90 nasal samples positive for the pH1N1 virus were deep-sequenced and analyzed to detect low-frequency variants (LFVs) and haplotypes. Parallel evolution of LFVs was seen in the hemagglutinin (HA) gene across three scales: among patients (33%), across years (22%), and at global scale. Remarkably, investigating the emergence of LFVs at the consensus level demonstrated that within-host virus evolution recapitulates evolutionary dynamics seen at the global scale. Analysis of virus diversity at the HA haplotype level revealed the clustering of low-frequency haplotypes from early 2015 with dominant strains of 2016, indicating rapid haplotype evolution. Haplotype sharing was also noticed in all years, strongly suggesting haplotype transmission among patients infected during a specific influenza season. Finally, more than half of patients with severe symptoms harbored a larger number of haplotypes, mostly in patients under the age of five. Therefore, patient age, haplotype diversity, and the presence of certain LFVs should be considered when interpreting illness severity. In addition to its importance in understanding virus evolution, sub-consensus virus diversity together with whole genome sequencing is essential to explain variabilities in clinical outcomes that cannot be explained by either analysis alone.
RNA病毒的多样性决定了它们在特定宿主、群体或环境中的进化。在此，我们报告了2015年至2017年三年间pH1N1病毒在宿主内和宿主间的共识和亚共识水平的多样性及其对疾病严重程度的影响。对总共90份pH1N1病毒呈阳性的鼻拭子样本进行了深度测序和分析，以检测低频变异（LFV）和单倍型。在血凝素（HA）基因中，LFV在三个尺度上呈现平行进化：患者之间（33%）、跨年（22%）以及全球尺度。值得注意的是，在共识水平上对LFV出现情况的研究表明，宿主内病毒进化重现了全球尺度上观察到的进化动态。对HA单倍型水平的病毒多样性分析揭示了2015年初低频单倍型与2016年优势毒株的聚类，表明单倍型快速进化。在所有年份中还注意到单倍型共享，这强烈表明在特定流感季节感染的患者之间存在单倍型传播。最后，超过一半有严重症状的患者携带了更多数量的单倍型，大多是五岁以下的患者。因此，在解释疾病严重程度时应考虑患者年龄、单倍型多样性以及某些LFV的存在。除了在理解病毒进化方面的重要性外，亚共识病毒多样性与全基因组测序对于解释单独任何一种分析都无法解释的临床结果变异性至关重要。
