VIDO-Intervac, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E3, Canada.
Viruses. 2013 Jan 21;5(1):295-320. doi: 10.3390/v5010295.
Respiratory syncytial virus (RSV) is the leading cause of infant bronchiolitis. The closely related pneumonia virus of mice (PVM) causes a similar immune-mediated disease in mice, which allows an analysis of host factors that lead to severe illness. This project was designed to compare the immune responses to lethal and sublethal doses of PVM strain 15 in Balb/c and C57Bl/6 mice. Balb/c mice responded to PVM infection with an earlier and stronger innate response that failed to control viral replication. Production of inflammatory cyto- and chemokines, as well as infiltration of neutrophils and IFN-γ secreting natural killer cells into the lungs, was more predominant in Balb/c mice. In contrast, C57Bl/6 mice were capable of suppressing both viral replication and innate inflammatory responses. After a sublethal infection, PVM-induced IFN-γ production by splenocytes was stronger early during infection and weaker at late time points in C57Bl/6 mice when compared to Balb/c mice. Furthermore, although the IgG levels were similar and the mucosal IgA titres lower, the virus neutralizing antibody titres were higher in C57Bl/6 mice than in Balb/c mice. Overall, the difference in susceptibility of these two strains appeared to be related not to an inherent T helper bias, but to the capacity of the C57Bl/6 mice to control both viral replication and the immune response elicited by PVM.
呼吸道合胞病毒（RSV）是婴儿细支气管炎的主要原因。密切相关的鼠肺炎病毒（PVM）在小鼠中引起类似的免疫介导疾病，这使得能够分析导致严重疾病的宿主因素。该项目旨在比较 Balb/c 和 C57Bl/6 小鼠对致死和亚致死剂量的 PVM 株 15 的免疫反应。Balb/c 小鼠对 PVM 感染的先天反应更早且更强，但未能控制病毒复制。炎性细胞因子和趋化因子的产生，以及中性粒细胞和 IFN-γ 分泌的自然杀伤细胞浸润到肺部，在 Balb/c 小鼠中更为明显。相比之下，C57Bl/6 小鼠能够抑制病毒复制和先天炎症反应。在亚致死感染后，与 Balb/c 小鼠相比，C57Bl/6 小鼠脾细胞产生的 PVM 诱导 IFN-γ 在感染早期更强，而在晚期较弱。此外，尽管 IgG 水平相似，粘膜 IgA 滴度较低，但 C57Bl/6 小鼠中的病毒中和抗体滴度高于 Balb/c 小鼠。总的来说，这两种菌株的易感性差异似乎不是与固有 T 辅助细胞偏向有关，而是与 C57Bl/6 小鼠控制病毒复制和 PVM 引起的免疫反应的能力有关。
