Lebrec H, Burleson G R
United States Environmental Protection Agency, Health Effects Research Laboratory, Research Triangle Park, North Carolina 27711.
Toxicology. 1994 Jul 1;91(2):179-88. doi: 10.1016/0300-483x(94)90143-0.
Each year influenza viruses are responsible for epidemic respiratory diseases with excess morbidity and mortality. The severity of influenza diseases ranges from mild upper respiratory tract infections to severe lower respiratory tract infections involving pneumonia, bronchiolitis and coincidental bacterial super-infections. The immune response to influenza viruses can be schematically divided into a cascade of non-specific and specific functions. These functions are involved at different well defined time points after infection. We describe in this manuscript three influenza models utilized in our laboratory: (i) a highly virulent influenza virus (influenza A/Hong Kong/8/68 (H3N2) virus) adapted to B6C3F1 mice, (ii) a mouse-adapted influenza A/Port Chalmers/1/73 (H3N2) virus, and (iii) a rat-adapted influenza virus (RAIV) model (influenza A/Port Chalmers/1/73 (H3N2)). This rat-adapted influenza model has been mainly utilized as a model to assess local immunotoxic effects of inhaled environmental pollutants such as phosgene. These host resistance models are also useful for assessing the effect of systemically-induced immunosuppression or immunomodulation by drugs or chemicals on the local pulmonary immune response to influenza virus. The comparison of these different models allowed two major conclusions: (a) viral replication and mortality are two different endpoints and are not necessarily linked (no mortality was observed with Port Chalmers virus in the mouse although the virus replicates to high titers in the lung with a kinetic pattern comparable to the one obtained with Hong Kong virus), (b) mortality, viral replication, and immune function assessment are different endpoints that can be used, depending on the question addressed.
每年，流感病毒都会引发具有较高发病率和死亡率的流行性呼吸道疾病。流感疾病的严重程度从轻度上呼吸道感染到严重的下呼吸道感染不等，后者包括肺炎、细支气管炎以及并发的细菌超级感染。对流感病毒的免疫反应可大致分为一系列非特异性和特异性功能。这些功能在感染后的不同明确时间点发挥作用。在本手稿中，我们描述了在我们实验室中使用的三种流感模型：（i）适应B6C3F1小鼠的高致病性流感病毒（甲型流感/香港/8/68（H3N2）病毒），（ii）适应小鼠的甲型流感/查尔姆斯港/1/73（H3N2）病毒，以及（iii）适应大鼠的流感病毒（RAIV）模型（甲型流感/查尔姆斯港/1/73（H3N2））。这种适应大鼠的流感模型主要被用作评估吸入环境污染物（如光气）的局部免疫毒性作用的模型。这些宿主抵抗力模型也有助于评估药物或化学物质引起的全身免疫抑制或免疫调节对流感病毒局部肺部免疫反应的影响。对这些不同模型的比较得出了两个主要结论：（a）病毒复制和死亡率是两个不同的终点，不一定相关（在小鼠中，查尔姆斯港病毒未观察到死亡率，尽管该病毒在肺部以与香港病毒相当的动力学模式复制到高滴度），（b）死亡率、病毒复制和免疫功能评估是不同的终点，可根据所解决的问题使用。
