Han Su Myat, Kubo Yoshiano, Robert Alexis, Baguelin Marc, Ariyoshi Koya
School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki 852-8523, Japan.
Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
Viruses. 2025 Jan 23;17(2):152. doi: 10.3390/v17020152.
Numerous studies have documented the evidence of virus-virus interactions at the population, host, and cellular levels. However, the impact of these interactions on the within-host diversity of influenza viral populations remains unexplored. Our study identified 13 respiratory viral pathogens from the nasopharyngeal swab samples (NPSs) of influenza-like-illness (ILI) patients during the 2012/13 influenza season using multiplex RT-PCR. Subsequent next-generation sequencing (NGS) of RT-PCR-confirmed influenza A infections revealed all samples as subtype A/H3N2. Out of the 2305 samples tested, 538 (23.3%) were positive for the influenza A virus (IAV), while rhinovirus (RV) and adenoviruses (Adv) were detected in 264 (11.5%) and 44 (1.9%) samples, respectively. Among these, the co-detection of more than one virus was observed in ninety-six samples, and five samples showed co-detections involving more than two viruses. The most frequent viral co-detection was IAV-RV, identified in 48 out of the 96 co-detection cases. Of the total samples, 150 were processed for whole-genome sequencing (WGS), and 132 met the criteria for intra-host single-nucleotide variant (iSNV) calling. Across the genome, 397 unique iSNVs were identified, with most samples containing fewer than five iSNVs at frequencies below 10%. Seven samples had no detectable iSNVs. Notably, the majority of iSNVs (86%) were unique and rarely shared across samples. We conducted a negative binomial regression analysis to examine factors associated with the number of iSNVs detected within hosts. Two age groups-elderly individuals (>64 years old) and school-aged children (6-18 years old)-were significantly associated with higher iSNV counts, with incidence rate ratios (IRR) of 1.80 (95% confidence interval [CI]: 1.09-3.06) and 1.38 (95% CI: 1.01-1.90), respectively. Our findings suggest a minor or negligible contribution of these viral co-detections to the evolution of influenza viruses. However, the data available in this study may not be exhaustive, warranting further, more in-depth investigations to conclusively determine the impact of virus-virus interactions on influenza virus genetic diversity.
众多研究已记录了病毒与病毒在种群、宿主及细胞水平相互作用的证据。然而,这些相互作用对流感病毒种群在宿主体内的多样性的影响仍未得到探索。我们的研究在2012/13流感季节,通过多重逆转录聚合酶链反应(RT-PCR)从流感样疾病(ILI)患者的鼻咽拭子样本(NPSs)中鉴定出13种呼吸道病毒病原体。随后对RT-PCR确认的甲型流感感染进行的下一代测序(NGS)显示,所有样本均为A/H3N2亚型。在检测的2305个样本中,538个(23.3%)甲型流感病毒(IAV)呈阳性,而鼻病毒(RV)和腺病毒(Adv)分别在264个(11.5%)和44个(1.9%)样本中被检测到。其中,在96个样本中观察到一种以上病毒的共同检测,5个样本显示共同检测涉及两种以上病毒。最常见的病毒共同检测是IAV-RV,在96例共同检测病例中有48例被鉴定出来。在所有样本中,150个样本进行了全基因组测序(WGS),132个样本符合宿主内单核苷酸变异(iSNV)检测标准。在整个基因组中,鉴定出397个独特的iSNV,大多数样本中iSNV数量少于5个,频率低于10%。7个样本未检测到iSNV。值得注意的是,大多数iSNV(86%)是独特的,很少在样本间共享。我们进行了负二项回归分析,以检查与宿主内检测到的iSNV数量相关的因素。两个年龄组——老年人(>64岁)和学龄儿童(6-18岁)——与较高的iSNV计数显著相关,发病率比(IRR)分别为1.80(95%置信区间[CI]:1.09-3.06)和1.38(95%CI:1.01-1.90)。我们的研究结果表明,这些病毒共同检测对流感病毒进化的贡献较小或可忽略不计。然而,本研究中的现有数据可能并不详尽,需要进一步进行更深入的调查,以最终确定病毒与病毒相互作用对流感病毒遗传多样性的影响。
Cochrane Database Syst Rev. 2023-1-30
Cochrane Database Syst Rev. 2018-2-1
Cochrane Database Syst Rev. 2020-10-19
Cochrane Database Syst Rev. 2018-2-1
Cochrane Database Syst Rev. 2012-1-18
Cochrane Database Syst Rev. 2022-5-20
J Virol. 2024-6-13
Curr Res Microb Sci. 2022-6-18
PLoS Pathog. 2021-9-2
Annu Rev Virol. 2020-9-29
Mol Biol Evol. 2020-5-1
Proc Natl Acad Sci U S A. 2019-12-26