Centro Nacional de Biotecnología, C.S.I.C. Darwin 3, Cantoblanco, Madrid, Spain.
PLoS One. 2013;8(1):e53515. doi: 10.1371/journal.pone.0053515. Epub 2013 Jan 10.
Pandemic 2009 H1N1 (pH1N1) influenza viruses caused mild symptoms in most infected patients. However, a greater rate of severe disease was observed in healthy young adults and children without co-morbid conditions. Here we tested whether influenza strains displaying differential virulence could be present among circulating pH1N1 viruses. The biological properties and the genotype of viruses isolated from a patient showing mild disease (M) or from a fatal case (F), both without known co-morbid conditions were compared in vitro and in vivo. The F virus presented faster growth kinetics and stronger induction of cytokines than M virus in human alveolar lung epithelial cells. In the murine model in vivo, the F virus showed a stronger morbidity and mortality than M virus. Remarkably, a higher proportion of mice presenting infectious virus in the hearts, was found in F virus-infected animals. Altogether, the data indicate that strains of pH1N1 virus with enhanced pathogenicity circulated during the 2009 pandemic. In addition, examination of chemokine receptor 5 (CCR5) genotype, recently reported as involved in severe influenza virus disease, revealed that the F virus-infected patient was homozygous for the deleted form of CCR5 receptor (CCR5Δ32).
2009 年甲型 H1N1（pH1N1）流感病毒在大多数感染患者中引起轻度症状。然而，在没有合并症的健康年轻成年人和儿童中，观察到更严重疾病的发生率更高。在这里，我们测试了是否在流行的 pH1N1 病毒中存在具有不同毒力的流感株。对来自表现为轻度疾病（M）或来自无已知合并症的致命病例（F）的患者的病毒的生物学特性和基因型进行了比较，无论是在体外还是体内。F 病毒在人肺泡肺上皮细胞中的生长动力学更快，细胞因子诱导作用更强。在体内的小鼠模型中，F 病毒比 M 病毒表现出更强的发病率和死亡率。值得注意的是，在感染 F 病毒的动物中，发现更多的小鼠在心脏中存在有感染性病毒。总之，这些数据表明，在 2009 年大流行期间，具有增强致病性的 pH1N1 病毒株在循环中。此外，对趋化因子受体 5（CCR5）基因型的检查，最近报道其与严重流感病毒疾病有关，显示感染 F 病毒的患者是 CCR5 受体（CCR5Δ32）缺失形式的纯合子。
