Molina Guido N, Tavarone Eugenia, Taboga Oscar, Molinari Paula
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), CABA, Argentina.
Instituto de Biotecnología, Centro Nacional de Investigaciones Agropecuarias (CNIA), INTA Castelar, Buenos Aires, Argentina.
PLoS One. 2016 Dec 29;11(12):e0168939. doi: 10.1371/journal.pone.0168939. eCollection 2016.
The budded phenotype (BV) of the baculovirus AcMNPV has been demonstrated to have strong immunostimulatory properties that are relevant for the development of vaccines and antiviral therapies. Although the occluded phenotype (ODV) shares the main structural proteins and its genome with BV, it has been poorly studied in mammals. In this study, we assessed the capacity of ODV to induce immune responses in mice. In contrast to BVs, ODVs failed to promote the secretion of IFN-gamma, IL-6 and Il-12 and to induce antiviral activity against VSV in the short term. Furthermore, ODVs were unable to induce cellular immunity against a coadministered antigen 7 days after inoculation. By analyzing the interaction of ODVs with BMDCs, we observed that although ODVs entered the cells reaching late and acidic endosomes, they did not induce their maturation. Finally, we also analyzed if BVs and ODVs followed different routes in the cell during the infection. BVs, but not ODVs, colocalized with the protein ovalbumin in compartments with the presence of proteases. The results suggest that structural differences could be responsible for their different destinies in the dendritic cell and this could lead to a different impact on the immune response.
杆状病毒AcMNPV的出芽型(BV)已被证明具有强大的免疫刺激特性,这与疫苗和抗病毒疗法的开发相关。尽管包涵体型(ODV)与BV共享主要结构蛋白及其基因组,但在哺乳动物中对其研究较少。在本研究中,我们评估了ODV在小鼠中诱导免疫反应的能力。与BVs相反,ODV在短期内未能促进IFN-γ、IL-6和Il-12的分泌,也未能诱导针对VSV的抗病毒活性。此外,接种7天后,ODV无法诱导针对共同给药抗原的细胞免疫。通过分析ODV与BMDCs的相互作用,我们观察到尽管ODV进入细胞并到达晚期酸性内体,但它们并未诱导其成熟。最后,我们还分析了感染期间BVs和ODV在细胞中是否遵循不同的途径。BVs而非ODV与存在蛋白酶的区室中的卵清蛋白共定位。结果表明,结构差异可能是它们在树突状细胞中不同命运的原因,这可能导致对免疫反应产生不同的影响。