Menne S, Maschke J, Lu M, Grosse-Wilde H, Roggendorf M
Institute of Virology, University of Essen, D-45122 Essen, Germany.
J Virol. 1998 Jul;72(7):6083-91. doi: 10.1128/JVI.72.7.6083-6091.1998.
The infection of woodchucks with woodchuck hepatitis virus (WHV) provides an experimental model to study early immune responses during hepadnavirus infection that cannot be tested in patients. The T-cell response of experimentally WHV-infected woodchucks to WHsAg, rWHcAg, and WHcAg peptides was monitored by observing 5-bromo-2'-deoxyuridine and [2-3H]adenine incorporation. The first T-cell responses were directed against WHsAg 3 weeks after infection; these were followed by responses to rWHcAg including the immunodominant T-cell epitope of WHcAg (amino acids 97 to 110). Maximal proliferative responses were detected when the animals seroconvered to anti-WHs and anti-WHc (week 6). A decrease in the T-cell response to viral antigens coincided with clearance of viral DNA. Polyclonal rWHcAg-specific T-cell lines were established 6, 12, 18, and 24 weeks postinfection, and their responses to WHcAg peptides were assessed. Five to seven peptides including the immunodominant epitope were recognized throughout the observation period (6 months). At 12 months after infection, T-cell responses to antigens and peptides were not detected. Reactivation of T-cell responses to viral antigens and peptides occurred within 7 days after challenge of animals with WHV. These results demonstrate that a fast and vigorous T-cell response to WHsAg, rWHcAg, and amino acids 97 to 110 of the WHcAg occurs within 3 weeks after WHV infection. The peak of this response was associated with viral clearance and may be crucial for recovery from infection. One year after infection, no proliferation of T cells in response to antigens was observed; however, the WHV-specific T-cell response was reactivated after challenge of woodchucks with WHV and may be responsible for protection against WHV reinfection.
土拨鼠感染土拨鼠肝炎病毒（WHV）为研究乙肝病毒感染期间的早期免疫反应提供了一个实验模型，而这在患者中无法进行测试。通过观察5-溴-2'-脱氧尿苷和[2-³H]腺嘌呤掺入情况，监测实验性感染WHV的土拨鼠对WHsAg、rWHcAg和WHcAg肽段的T细胞反应。感染后3周，首次T细胞反应针对WHsAg；随后是对rWHcAg的反应，包括WHcAg的免疫显性T细胞表位（氨基酸97至110）。当动物血清转化为抗-WHs和抗-WHc时（第6周），检测到最大增殖反应。对病毒抗原的T细胞反应降低与病毒DNA清除同时发生。在感染后6、12、18和24周建立了多克隆rWHcAg特异性T细胞系，并评估了它们对WHcAg肽段的反应。在整个观察期（6个月）内，识别出包括免疫显性表位在内的5至7个肽段。感染后12个月，未检测到对抗原和肽段的T细胞反应。在用WHV攻击动物后7天内，对病毒抗原和肽段的T细胞反应重新激活。这些结果表明，在WHV感染后3周内，对WHsAg、rWHcAg以及WHcAg的氨基酸97至110会出现快速且强烈的T细胞反应。这种反应的峰值与病毒清除相关，可能对从感染中恢复至关重要。感染一年后，未观察到T细胞对抗原的增殖反应；然而，在用WHV攻击土拨鼠后，WHV特异性T细胞反应重新激活，可能负责预防WHV再次感染。
