Meerts P, Van Gucht S, Cox E, Vandebosch A, Nauwynck H J
Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Belgium.
Viral Immunol. 2005;18(2):333-41. doi: 10.1089/vim.2005.18.333.
Porcine circovirus 2 (PCV2) replication is characterized by high variation among infected pigs. This study investigated the role of immunologic responses in causing this variation. Twelve gnotobiotic pigs were inoculated with PCV2. Four of these pigs were treated with cyclosporin A (CysA) to monitor the effect of the adaptive immunity on the development of the PCV2 infection. Through lymph node biopsies at 10, 15, and 21 days postinoculation (DPI), PCV2 replication in lymphoid tissues was monitored. The production of total PCV2-specific and PCV2-neutralizing antibodies was followed, together with interferon-gamma (IFN-gamma) mRNA expression levels in peripheral blood monocytes as a marker for cellular immunity. In general, the CysA-treated pigs showed the highest PCV2 titers, indicating that the adaptive immunity is necessary to restrain PCV2 replication. Three different PCV2 replication patterns were observed in non-CysA-treated pigs. Pattern 1: In two pigs, PCV2 was not detected. They had the highest neutralizing antibody titers, appearing from 15 DPI. In these pigs a good cellular response was indicated by a peak in IFN-gamma mRNA at 15 DPI. Pattern 2: Five pigs contained low to moderate PCV2 titers at 15 DPI, remaining constant or decreasing towards 21 DPI. Lower neutralizing antibody titers were observed and no rise in IFN-gamma was detected. Pattern 3: In one pig, a low PCV2 titer at 15 DPI dramatically increased toward 21 DPI. Although an antibody response against PCV2 was mounted, no PCV2-neutralizing antibodies were detected. This pig also showed no rise in IFN-gamma. The study findings indicate that variation in the onset of the adaptive immunity may account for variation in PCV2 replication among pigs. Absence of PCV2-neutralizing antibodies may be an important factor in the development of an increased virus replication.
猪圆环病毒2型（PCV2）的复制特点是在受感染猪之间存在高度变异。本研究调查了免疫反应在导致这种变异中所起的作用。给12头无菌猪接种PCV2。其中4头猪用环孢素A（CysA）进行处理，以监测适应性免疫对PCV2感染发展的影响。通过在接种后第10、15和21天（dpi）进行淋巴结活检，监测淋巴组织中PCV2的复制情况。跟踪总PCV2特异性抗体和PCV2中和抗体的产生，以及外周血单核细胞中干扰素-γ（IFN-γ）mRNA表达水平作为细胞免疫的标志物。总体而言，用CysA处理的猪显示出最高的PCV2滴度，表明适应性免疫对于抑制PCV2复制是必要的。在未用CysA处理的猪中观察到三种不同的PCV2复制模式。模式1：在两头猪中未检测到PCV2。它们具有最高的中和抗体滴度，从15 dpi开始出现。在这些猪中，15 dpi时IFN-γ mRNA出现峰值表明细胞反应良好。模式2：五头猪在15 dpi时PCV2滴度低至中等，在21 dpi时保持恒定或下降。观察到较低的中和抗体滴度，且未检测到IFN-γ升高。模式3：在一头猪中，15 dpi时低PCV2滴度在21 dpi时急剧增加。尽管产生了针对PCV2的抗体反应，但未检测到PCV2中和抗体。这头猪也未显示出IFN-γ升高。研究结果表明，适应性免疫起始的差异可能是猪之间PCV2复制差异的原因。缺乏PCV2中和抗体可能是病毒复制增加发展过程中的一个重要因素。
