Kekarainen Tuija, Montoya Maria, Dominguez Javier, Mateu Enric, Segalés Joaquim
Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Vet Immunol Immunopathol. 2008 Jul 15;124(1-2):41-9. doi: 10.1016/j.vetimm.2008.01.031. Epub 2008 Jan 21.
Porcine circovirus type 2 (PCV2) is a single-stranded circular DNA virus infecting domestic pigs worldwide. Interaction of this virus with the immune system apparently modulates the immune response of the host. In the present study, the implication of different components of PCV2 in the modulation of the immune response of the host were investigated by using PCV2 viral-like particles (VLPs) and 16 novel oligodeoxyribonucleotides containing CpG motifs (CpG-ODNs) based on the PCV2 genomic sequence. The role of these viral components was studied by evaluating the cytokine profiles (IFN-alpha, IFN-gamma, IL-10, IL-2 and IL-12) on porcine peripheral mononuclear cell (PBMC) and bone marrow-derived dendritic cell (BMDC) cultures. Also, the effect of PCV2 and its elements were examined in recall antigen (pseudorabies virus, PRV) responses. While PCV2 was a potent inducer of IL-10 by PBMCs, such effect was not observed using CpG-ODNs or VLPs. However, IFN-gamma and IL-2 production by recall antigen was repressed in presence of PCV2 and most of the studied CpG-ODNs. VLPs did not have such repressive effect. In BMDC cultures, PCV2 and most of CpG-ODNs were able to inhibit IFN-alpha secretion induced by PRV. Interestingly, CpG-ODNs with inhibitory effect were located within the PCV2 Rep gene. Additionally, PCV2 virus was a very strong IL-12 inducer in BMDC cultures. Whereas, IFN-alpha modulation on BMDC after PCV2 VLP treatment was neglectable, PCV2 VLPs were potent IL-12 inducers. Our data shows that PCV2 viral elements can distinctly regulate cytokine production depending on the cell population studied. Thus, the final immune response upon PCV2 infection seems to depend on the fine balance between the regulatory elements present in viral DNA and structural protein within the host immune system.
猪圆环病毒2型（PCV2）是一种单链环状DNA病毒，可感染全球范围内的家猪。这种病毒与免疫系统的相互作用显然会调节宿主的免疫反应。在本研究中，基于PCV2基因组序列，使用PCV2病毒样颗粒（VLP）和16种含CpG基序的新型寡脱氧核糖核苷酸（CpG-ODN），研究了PCV2不同组分在调节宿主免疫反应中的作用。通过评估猪外周血单个核细胞（PBMC）和骨髓来源的树突状细胞（BMDC）培养物中的细胞因子谱（IFN-α、IFN-γ、IL-10、IL-2和IL-12），研究了这些病毒组分的作用。此外，还检测了PCV2及其元件在回忆抗原（伪狂犬病病毒，PRV）反应中的作用。虽然PCV2是PBMC诱导IL-10的强效诱导剂，但使用CpG-ODN或VLP未观察到这种效果。然而，在存在PCV2和大多数研究的CpG-ODN的情况下，回忆抗原诱导的IFN-γ和IL-2产生受到抑制。VLP没有这种抑制作用。在BMDC培养物中，PCV2和大多数CpG-ODN能够抑制PRV诱导的IFN-α分泌。有趣的是，具有抑制作用的CpG-ODN位于PCV2 Rep基因内。此外，PCV2病毒是BMDC培养物中非常强的IL-12诱导剂。而PCV2 VLP处理后对BMDC的IFN-α调节作用可忽略不计，PCV2 VLP是强效的IL-12诱导剂。我们的数据表明，PCV2病毒元件可根据所研究的细胞群体明显调节细胞因子的产生。因此，PCV2感染后的最终免疫反应似乎取决于病毒DNA中的调节元件与宿主免疫系统中的结构蛋白之间的精细平衡。
