Department of Medical Genomics Research, King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
Department of Medical Genomics Research, King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia; Department of Pathology & Laboratory Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia; King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
J Infect Public Health. 2019 Jul-Aug;12(4):557-567. doi: 10.1016/j.jiph.2019.01.067. Epub 2019 Feb 21.
The triple assortment influenza A(H1N1) virus emerged in spring 2009 and disseminated worldwide, including Saudi Arabia. This study was carried out to characterize Saudi influenza isolates in relation to the global strains and to evaluate the potential role of mutated residues in transmission, adaptation, and the pathogenicity of the virus.
Nasopharyngeal samples (n = 6492) collected between September 2009 to March 2011 from patients with influenza-like illness were screened by PCR for influenza A(H1N1). Phylogenetic and Molecular evolutionary analysis were carried out to place the Saudi strains in relation to the global strains followed by Mutation analysis of surface and internal proteins.
Concatenated whole-genome phylogenetic analysis along with hemagglutinin (HA) signature changes, that is, Aspartic Acid (D) at position 187, P83S, S203T, and R223Q confirmed that the Saudi strains belong to the antigenic category of A/California/07/2009. However, phylogenetic analysis revealed unusual strains of A(H1N1) circulating in Saudi Arabia, not belonging to any of known clades, appearing in five distinct groups well supported by group-specific mutations and novel mutation complexes. These cases had characteristic inter- and intragroup substitution patterns while few of their closest matches showed up as sporadic cases the world over. Specific mutation patterns were detected within the functional domains of internal proteins PB2, PB1, PA, NP, NS1, and M2 having a putative role in viral fitness and virulence. Bayesian coalescent MCMC analysis revealed that Saudi strains belonged to cluster 2 of A(H1N1)pdm09 and spread a month later as compared to other strains of this cluster.
Influenza outbreak in Saudi Arabia during 2009-2011 was caused by atypical strains of influenza A(H1N1)pdm09, probably introduced in this community on multiple occasions. To understand the antigenic significance of these novel point mutations and mutation complexes require functional studies, which will be crucial for risk assessment of emergent strains and defining infection control measures.
三重组合甲型 H1N1 流感病毒于 2009 年春季出现并在全球范围内传播,包括沙特阿拉伯。本研究旨在对沙特流感分离株进行特征分析,以了解其与全球株的关系,并评估突变残基在病毒传播、适应和致病性方面的潜在作用。
从 2009 年 9 月至 2011 年 3 月期间因流感样疾病就诊的患者的鼻咽拭子标本中采集了 6492 份样本,采用 PCR 方法对甲型 H1N1 进行了筛查。对沙特分离株进行了系统发育和分子进化分析,以了解其与全球株的关系,然后对表面和内部蛋白进行突变分析。
串联全基因组系统发育分析以及血凝素(HA)特征性变化,即位置 187 的天冬氨酸(D)、P83S、S203T 和 R223Q,证实沙特分离株属于 A/加利福尼亚/07/2009 的抗原类别。然而,系统发育分析显示,在沙特阿拉伯流行的甲型 H1N1 存在不寻常的毒株,它们不属于任何已知的分支,在五个不同的群组中出现,这些群组得到了群组特异性突变和新的突变复合物的有力支持。这些病例具有特征性的组内和组间替换模式,而它们的少数最接近的匹配病例则在世界各地零星出现。在内部蛋白 PB2、PB1、PA、NP、NS1 和 M2 的功能域中检测到特定的突变模式,这些突变模式可能与病毒适应性和毒力有关。贝叶斯共聚合 MCMC 分析显示,沙特分离株属于 A(H1N1)pdm09 的聚类 2,与该聚类的其他株相比,传播时间晚了一个月。
2009-2011 年沙特流感爆发是由甲型 H1N1)pdm09 的非典型株引起的,这些株可能多次在该社区中传入。要了解这些新的点突变和突变复合物的抗原意义,需要进行功能研究,这对于评估新出现的菌株的风险和确定感染控制措施至关重要。