Bird P, Blacklaws B, Reyburn H T, Allen D, Hopkins J, Sargan D, McConnell I
Department of Veterinary Pathology, University of Edinburgh, Summerhall, Scotland.
J Virol. 1993 Sep;67(9):5187-97. doi: 10.1128/JVI.67.9.5187-5197.1993.
Infections caused by lentiviruses, including human immunodeficiency virus, are characterized by slowly progressive disease in the presence of a virus-specific immune response. The earliest events in the virus-host interaction are likely to be important in determining disease establishment and progression, and the kinetics of these early events following lentiviral infection are described here. Lymphatic cannulation in the sheep has been used to monitor both the virus and the immune response in efferent lymph after infection of the node with maedi-visna virus (MVV). Viral replication and dissemination could be detected and consisted of a wave of MVV-infected cells leaving the node around 9 to 18 days postinfection. No cell-free virus was recovered despite the fact that soluble MVV p25 was detected in lymph plasma. The maximum frequency of MVV-infected cells was only 11 in 10(6) but over the first 20 days of infection amounted to greater than 10(4) virus-infected cells leaving the node. There was a profound increase in the output of activated lymphoblast from the lymph nodes of infected sheep, characterized by an increased percentage of CD8+ lymphoblasts. All of the CD8+ lymphoblasts at the peak of the response expressed both major histocompatibility complex class II DR and DQ molecules but not interleukin-2 receptor (CD25). The in vitro proliferative response of efferent lymph cells existing the node after challenge with MVV to both recombinant human interleukin-2 and the mitogen concanavalin A was decreased between days 8 and 16 postinfection, and a specific proliferative response to MVV was not detected until after day 15. Despite the high level of CD8+ lymphoblasts in efferent lymph, direct MVV-specific cytotoxic activity was demonstrated in only one of the five MVV-challenged sheep. MVV-specific antibody responses, including neutralization and MVV p25 immune complexes in efferent lymph, were detectable during the major period of virus dissemination. The relationship of these findings to the evasion of the host's acute immune response by MVV is discussed.
慢病毒（包括人类免疫缺陷病毒）引起的感染，其特征是在存在病毒特异性免疫反应的情况下疾病进展缓慢。病毒与宿主相互作用的最早事件可能对疾病的建立和进展起重要作用，本文描述了慢病毒感染后这些早期事件的动力学。绵羊的淋巴管插管已被用于监测在用梅迪 - 维斯纳病毒（MVV）感染淋巴结后，输出淋巴液中的病毒和免疫反应。可以检测到病毒复制和传播，其表现为一波受MVV感染的细胞在感染后约9至18天离开淋巴结。尽管在淋巴血浆中检测到可溶性MVV p25，但未回收无细胞病毒。受MVV感染细胞的最大频率仅为每10⁶个细胞中有11个，但在感染的前20天内，有超过10⁴个受病毒感染的细胞离开淋巴结。受感染绵羊淋巴结中活化淋巴母细胞的输出显著增加，其特征是CD8⁺淋巴母细胞的百分比增加。反应高峰期所有的CD8⁺淋巴母细胞均表达主要组织相容性复合体II类DR和DQ分子，但不表达白细胞介素 - 2受体（CD25）。在用MVV攻击后离开淋巴结的输出淋巴细胞对重组人白细胞介素 - 2和促有丝分裂原刀豆球蛋白A的体外增殖反应在感染后第8天至16天之间降低，并且直到第15天后才检测到对MVV的特异性增殖反应。尽管输出淋巴液中CD8⁺淋巴母细胞水平很高，但在五只接受MVV攻击的绵羊中只有一只表现出直接的MVV特异性细胞毒性活性。在病毒传播的主要时期可检测到MVV特异性抗体反应，包括输出淋巴液中的中和反应和MVV p25免疫复合物。讨论了这些发现与MVV逃避宿主急性免疫反应的关系。
