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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Virus-like interference in the latency and prevention of Creutzfeldt-Jakob disease.
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Virus-like interference in the latency and prevention of Creutzfeldt-Jakob disease.

机译:类病毒干扰克雅氏病的潜伏期和预防。

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We previously showed that intracerebral (ic) inoculation of the attenuated SY strain of Creutzfeld-Jakob disease in mice could delay clinical signs and widespread neuropathology evoked by subsequent ic challenge with the more virulent FU strain. Using lower doses of SY and FU ic, we here demonstrate that mice can be protected well into old age without demonstrable neuropathology or pathologic prion protein (PrP-res). In contrast, parallel FU only controls became terminally diseased 1 year earlier. To determine whether factors elaborated in response to SY might be part of this effect, we evaluated brain and serum samples from additional parallel mice at 90 days after SY infection and just before FU challenge. The infectivity of FU preparations was significantly reduced by mixing with these fresh SY brain homogenates but not by mixing with SY serum samples, suggesting that brain cells were elaborating labile inhibitory factors that were part of the protective response. SY infectivity was too low to be detected in these brain homogenates. Although suppression could be overcome by higher FU doses ic, strong protection against maximal doses of FU was observed by using i.v. inoculations. Because myeloid microglia are infectious and also elaborate many factors in response to the foreign Creutzfeld-Jakob disease agent, it is likely that innate immunity underlies the profound protection shown here. In principle, it should be possible to artificially stimulate relevant myeloid pathways to better prevent andor delay the clinical and pathological sequelae of these infections.
机译:我们先前显示,小鼠的Creutzfeld-Jakob病减毒SY株的脑内(ic)接种可能会延迟临床症状,并随后通过使用更具毒性的FU株进行ic激发而引起广泛的神经病理学变化。使用较低剂量的SY和FU ic,我们在此证明,无需明显的神经病理或病理性pr病毒蛋白(PrP-res),小鼠就可以得到很好的保护。相反,仅平行FU对照在1年前患上了绝症。为了确定对SY的应答所阐述的因素是否可能是这种作用的一部分,我们在SY感染后90天和FU攻击之前评估了来自其他平行小鼠的脑和血清样品。通过与这些新鲜的SY脑匀浆混合而不是通过与SY血清样品混合,FU制剂的传染性显着降低,这表明脑细胞正在发挥不稳定的抑制因子,这是保护性反应的一部分。 SY感染力太低,无法在这些脑匀浆中检测到。尽管较高的FU剂量可以克服抑制作用,但通过使用i.v.可以观察到针对最大剂量FU的强大保护作用。接种。由于髓样小胶质细胞具有传染性,并且还针对外国Creutzfeld-Jakob病原体精心设计了许多因素,因此,固有免疫可能是此处所示深层保护的基础。原则上,应该有可能人工刺激相关的髓样途径,以更好地预防和/或延缓这些感染的临床和病理后遗症。

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