Department of Pathophysiology, College of Veterinary Medicine, China Agricultural University, 100193, Beijing, People's Republic of China.
Arch Virol. 2010 Feb;155(2):187-95. doi: 10.1007/s00705-009-0560-0. Epub 2009 Nov 28.
H9N2 avian influenza viruses have repeatedly caused infections in swine and humans in some countries. The purpose of the present study was to evaluate the pulmonary pathology caused by H9N2 viral infection in mice. Six- to eight-week-old BALB/c mice were infected intranasally with 1 x 10(4) MID(50) of A/Chicken/Hebei/4/2008(H9N2) virus. Clinical signs, pathological changes and viral replication in lungs, arterial blood gas, and cytokines in bronchoalveolar lavage fluid (BALF) were observed at different time points after infection. A control group was infected intranasally with noninfectious allantoic fluid. H9N2-infected mice exhibited severe respiratory syndrome, with a mortality rate of 60%. Gross observations showed that infected lungs were highly edematous. Major histopathological changes in infected lungs included diffuse pneumonia and alveolar damage, with neutrophil-dominant inflammatory cellular infiltration, interstitial and alveolar edema, hemorrhage, and severe bronchiolitis/peribronchiolitis. In addition, H9N2 viral infection resulted in severe progressive hypoxemia, lymphopenia, and a significant increase in neutrophils, tumor necrosis factor-alpha and interleukin-6 in BALF. The features described above satisfy the criteria for acute respiratory distress syndrome (ARDS). Our data show that H9N2 viral infection resulted in ARDS in mice, and this may facilitate studies of the pathogenesis of future potential H9N2 disease in humans.
H9N2 禽流感病毒已在一些国家多次导致猪和人类感染。本研究旨在评估 H9N2 病毒感染小鼠引起的肺部病理学变化。6 至 8 周龄 BALB/c 小鼠经鼻腔感染 1×10(4) MID(50)的 A/鸡/河北/4/2008(H9N2)病毒。感染后不同时间点观察临床症状、肺部病理变化和病毒复制、动脉血气、支气管肺泡灌洗液（BALF）中的细胞因子。对照组经鼻腔感染非感染性鸡胚尿囊液。H9N2 感染小鼠出现严重呼吸综合征，死亡率为 60%。大体观察可见感染肺高度水肿。感染肺的主要组织病理学变化包括弥漫性肺炎和肺泡损伤，以中性粒细胞为主的炎症细胞浸润、间质和肺泡水肿、出血和严重细支气管炎/细支气管周围炎。此外，H9N2 病毒感染导致严重进行性低氧血症、淋巴细胞减少和 BALF 中肿瘤坏死因子-α和白细胞介素-6 显著增加。上述特征符合急性呼吸窘迫综合征（ARDS）的标准。我们的数据表明，H9N2 病毒感染导致小鼠发生 ARDS，这可能有助于研究未来人类潜在 H9N2 疾病的发病机制。
