Lehmann C, Sprenger H, Nain M, Bacher M, Gemsa D
Institute of Immunology, Philipps University, Marburg, Germany.
Res Virol. 1996 Mar-Jun;147(2-3):123-30. doi: 10.1016/0923-2516(96)80226-3.
Human monocytes and murine macrophages were found to be susceptible to influenza A virus infection. We could show that virus was absorbed and de novo virus protein synthesis was initiated, but actual virus replication was extremely low; 24-36 h after infection, monocytes and macrophages died of apoptosis. Before cell death, an influenza A virus infection induced strong mRNA accumulation of cytokines: tumour necrosis factor-alpha (TNF alpha), interleukin-1 (IL1) and IL6. However, the translation into bioactive cytokine protein was rather low, and high cytokine production was only found when a secondary signal such as LPS was added. Influenza A virus infection of mononuclear phagocytes displayed a characteristic feature at the level of cytokine gene transcription which was not found with other viruses such as vesicular stomatitis virus: in addition to the regular 1.7-kb TNF alpha mRNA, a high molecular weight (hmw) TNF alpha mRNA of 2.4 kb was detected. This hmw TNF alpha mRNA did not contain intron or intergenic region elements, was polyadenylated and carried the regular 5' and 3' untranslated regions. The generation of hmw TNF alpha mRNA required exposure to fully infectious influenza A virus, since virus inactivation at 56 degrees C induced only regular and not hmw TNF alpha mRNA. Whether this unique hmw TNF alpha mRNA represents a virus-induced abnormality or only a superinduction of an otherwise minor TNF alpha transcript, and whether this mRNA species codes for a biologically active product, remain to be further studied.
研究发现人类单核细胞和小鼠巨噬细胞易受甲型流感病毒感染。我们能够证明病毒被吸收且从头开始的病毒蛋白合成启动，但实际病毒复制极低；感染后24 - 36小时，单核细胞和巨噬细胞死于凋亡。在细胞死亡前，甲型流感病毒感染诱导细胞因子的mRNA大量积累：肿瘤坏死因子-α（TNFα）、白细胞介素-1（IL1）和IL6。然而，向生物活性细胞因子蛋白的翻译相当低，只有当添加诸如脂多糖（LPS）等二级信号时才会发现高细胞因子产生。单核吞噬细胞的甲型流感病毒感染在细胞因子基因转录水平表现出一种特征，这在诸如水泡性口炎病毒等其他病毒中未发现：除了常规的1.7kb TNFα mRNA外，还检测到2.4kb的高分子量（hmw）TNFα mRNA。这种hmw TNFα mRNA不包含内含子或基因间区域元件，进行了多聚腺苷酸化并带有常规的5'和3'非翻译区。hmw TNFα mRNA的产生需要暴露于完全感染性的甲型流感病毒，因为在56℃下病毒失活仅诱导常规而非hmw TNFα mRNA。这种独特的hmw TNFα mRNA是代表病毒诱导的异常还是仅仅是原本少量的TNFα转录本的超诱导，以及这种mRNA种类是否编码一种生物活性产物，仍有待进一步研究。
