Jayasekera Jerome P, Vinuesa Carola G, Karupiah Gunasegaran, King Nicholas J C
Department of Pathology, Bosch Institute, School of Biomedical Sciences, Blackburn Building D06, University of Sydney, NSW 2006, Australia.
Division of Immunology and Genetics, John Curtin School of Medical Research (JCSMR), Australian National University, Canberra, ACT 2601, Australia.
J Gen Virol. 2006 Nov;87(Pt 11):3361-3371. doi: 10.1099/vir.0.82131-0.
NOS2 gene-deficient (NOS2(-/-)) mice are less susceptible than wild-type (NOS2(+/+)) mice to infection with Influenza A virus. Virus titres in the lungs of influenza-infected NOS2(-/-) mice are significantly lower than those in NOS2(+/+) mice, with enhanced viral clearance in NOS2(-/-) mice dependent on gamma interferon (IFN-gamma). The current study was undertaken to ascertain the role of specific components of the immune response in promoting virus clearance in influenza-infected NOS2(-/-) mice. Levels of T cell- and natural killer cell-mediated cytotoxicity in the lungs of virus-infected mice were not significantly different between NOS2(+/+) and NOS2(-/-) mice. However, virus-infected NOS2(-/-) mice produced higher levels of virus-specific IgG2a antibody. Furthermore, more viable B cells and plasmablasts, along with greater levels of IFN-gamma, were found in NOS2(-/-) splenocyte cultures stimulated with B-cell mitogens. In addition to the early reduction in virus titres, clinical symptoms and proinflammatory cytokine production were attenuated in NOS2(-/-) mice. Thus, NOS2(-/-) B cells are capable of responding rapidly to influenza virus infection by proliferating and preferentially producing antibody of the IgG2a subtype. The relationship between viral load and the development of immunopathology is discussed.
一氧化氮合酶2基因缺陷（NOS2(-/-)）小鼠比野生型（NOS2(+/+)）小鼠更不易感染甲型流感病毒。感染流感的NOS2(-/-)小鼠肺中的病毒滴度显著低于NOS2(+/+)小鼠，NOS2(-/-)小鼠中病毒清除增强依赖于γ干扰素（IFN-γ）。当前研究旨在确定免疫反应的特定成分在促进感染流感的NOS2(-/-)小鼠清除病毒中的作用。在感染病毒的小鼠肺中，NOS2(+/+)和NOS2(-/-)小鼠的T细胞和自然杀伤细胞介导的细胞毒性水平没有显著差异。然而，感染病毒的NOS2(-/-)小鼠产生了更高水平的病毒特异性IgG2a抗体。此外，在用B细胞有丝分裂原刺激的NOS2(-/-)脾细胞培养物中发现了更多存活的B细胞和成浆细胞，以及更高水平的IFN-γ。除了病毒滴度早期降低外，NOS2(-/-)小鼠的临床症状和促炎细胞因子产生也有所减轻。因此，NOS2(-/-) B细胞能够通过增殖并优先产生IgG2a亚型抗体对流感病毒感染迅速做出反应。本文还讨论了病毒载量与免疫病理学发展之间的关系。
