Two Distinctive Phenotypes of AcMNPV Display Different Immune Abilities and Intracellular Destiny

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（Autographa californica multiple nucleopolyhedrovirus）的出芽型病毒体（budded phenotype, BV）已被证实具备较强的免疫刺激活性，该特性与疫苗及抗病毒疗法的开发息息相关。尽管包埋型病毒体（occluded phenotype, ODV）与BV共享主要结构蛋白与基因组，但针对其在哺乳动物中的研究仍相对匮乏。本研究评估了ODV在小鼠体内诱导免疫应答的能力。与BV不同，ODV无法在短期内促进干扰素γ（IFN-γ）、白细胞介素6（IL-6）及白细胞介素12（IL-12）的分泌，也不能诱导针对水疱性口炎病毒（vesicular stomatitis virus, VSV）的抗病毒活性。此外，接种7天后，ODV亦无法诱导针对共递送抗原的细胞免疫应答。通过分析ODV与骨髓源树突状细胞（bone marrow-derived dendritic cells, BMDCs）的相互作用，我们观察到尽管ODV可侵入细胞并抵达晚期酸性内体，但无法诱导树突状细胞成熟。最后，我们还探究了BV与ODV在感染过程中是否采取不同的细胞内通路：仅BV可与含有蛋白酶的胞内区室中的卵清蛋白（ovalbumin）发生共定位。上述结果表明，结构差异或是二者在树突状细胞内命运迥异的原因，而这也可能导致其对免疫应答产生截然不同的影响。