Southern Research Institute, Birmingham, AL 35205, USA.
Virol J. 2010 Jul 9;7:149. doi: 10.1186/1743-422X-7-149.
Every year, influenza viruses infect approximately 5-20% of the population in the United States leading to over 200,000 hospitalizations and 36,000 deaths from flu-related complications. In this study, we characterized the immune and pathological progression of a seasonal strain of H1N1 influenza virus, A/Brisbane/59/2007 in a ferret model. The immune response of the animals showed a dose-dependent increase with increased virus challenge, as indicated by the presence of virus specific IgG, IgM, and neutralizing antibodies. Animals infected with higher doses of virus also experienced increasing severity of clinical symptoms and fever at 2 days post-infection (DPI). Interestingly, weight loss was more pronounced in animals infected with lower doses of virus compared to those infected with a higher dose; these results were consistent with viral titers of swabs collected from the nares, but not the throat. Analyzed specimens included nasal and throat swabs from 1, 3, 5, and 7 DPI as well as tissue samples from caudal lung and nasal turbinates. Viral titers of the swab samples in all groups were higher on 1 and 3 DPI and returned to baseline levels by 7 DPI. Analysis of nasal turbinates indicated presence of virus at 3 DPI in all infected groups, whereas virus was only detected in the lungs of animals in the two highest dose groups. Histological analysis of the lungs showed a range of pathology, such as chronic inflammation and bronchial epithelial hypertrophy. The results provided here offer important endpoints for preclinical testing of the efficacy of new antiviral compounds and experimental vaccines.
每年,流感病毒都会感染美国约 5-20%的人口,导致超过 20 万人住院治疗,3.6 万人因流感相关并发症死亡。在这项研究中,我们在雪貂模型中对季节性 H1N1 流感病毒株 A/Brisbane/59/2007 的免疫和病理进展进行了特征描述。动物的免疫反应随着病毒挑战的增加呈剂量依赖性增加,这表现为存在病毒特异性 IgG、IgM 和中和抗体。感染高剂量病毒的动物在感染后 2 天(DPI)也经历了越来越严重的临床症状和发热。有趣的是,与感染高剂量病毒的动物相比,感染低剂量病毒的动物体重减轻更为明显;这些结果与从鼻腔而非喉咙采集的拭子中的病毒滴度一致。分析的标本包括感染后 1、3、5 和 7 天的鼻腔和喉咙拭子以及尾肺和鼻甲骨组织样本。所有组的拭子样本的病毒滴度在 1 天和 3 天最高,然后在 7 天恢复到基线水平。对鼻甲骨的分析表明,所有感染组在 3 天都存在病毒,而在两个最高剂量组的动物肺部只检测到病毒。对肺部的组织学分析显示出一系列病理学变化,如慢性炎症和支气管上皮细胞肥大。这里提供的结果为新抗病毒化合物和实验性疫苗的临床前疗效测试提供了重要的终点。