UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France.
PLoS Pathog. 2012;8(6):e1002782. doi: 10.1371/journal.ppat.1002782. Epub 2012 Jun 21.
It is now clearly established that the transfusion of blood from variant CJD (v-CJD) infected individuals can transmit the disease. Since the number of asymptomatic infected donors remains unresolved, inter-individual v-CJD transmission through blood and blood derived products is a major public health concern. Current risk assessments for transmission of v-CJD by blood and blood derived products by transfusion rely on infectious titers measured in rodent models of Transmissible Spongiform Encephalopathies (TSE) using intra-cerebral (IC) inoculation of blood components. To address the biological relevance of this approach, we compared the efficiency of TSE transmission by blood and blood components when administrated either through transfusion in sheep or by intra-cerebral inoculation (IC) in transgenic mice (tg338) over-expressing ovine PrP. Transfusion of 200 µL of blood from asymptomatic infected donor sheep transmitted prion disease with 100% efficiency thereby displaying greater virulence than the transfusion of 200 mL of normal blood spiked with brain homogenate material containing 10³ID₅₀ as measured by intracerebral inoculation of tg338 mice (ID₅₀ IC in tg338). This was consistent with a whole blood titer greater than 10³·⁶ID₅₀ IC in tg338 per mL. However, when the same blood samples were assayed by IC inoculation into tg338 the infectious titers were less than 32 ID per mL. Whereas the transfusion of crude plasma to sheep transmitted the disease with limited efficacy, White Blood Cells (WBC) displayed a similar ability to whole blood to infect recipients. Strikingly, fixation of WBC with paraformaldehyde did not affect the infectivity titer as measured in tg338 but dramatically impaired disease transmission by transfusion in sheep. These results demonstrate that TSE transmission by blood transfusion can be highly efficient and that this efficiency is more dependent on the viability of transfused cells than the level of infectivity measured by IC inoculation.
现在已经明确，从变异型克雅氏病（v-CJD）感染者中输血可以传播这种疾病。由于无症状感染供体的数量尚未确定，因此通过血液和血液制品在个体间传播 v-CJD 是一个主要的公共卫生关注点。目前，通过输血传播 v-CJD 的风险评估依赖于使用经颅内（IC）接种血液成分的传染性滴度在传染性海绵状脑病（TSE）的啮齿动物模型中进行测量。为了解决这种方法的生物学相关性，我们比较了通过输血或经颅内接种（IC）在过度表达绵羊朊病毒蛋白的转基因小鼠（tg338）中，血液和血液成分传播 TSE 的效率。从无症状感染供体绵羊中输血 200 µL 的血液以 100%的效率传播朊病毒疾病，因此显示出比输血 200 mL 含有 10³ID₅₀ 的脑匀浆材料更毒力，这是通过经颅内接种 tg338 小鼠（tg338 中的 ID₅₀ IC）来测量的。这与每毫升 tg338 中的全血滴度大于 10³·⁶ID₅₀ IC 一致。然而，当通过 IC 接种将相同的血液样本进行检测时，感染性滴度小于每毫升 32 ID。虽然向绵羊输注粗制血浆可以传播疾病，但效率有限，白细胞（WBC）显示出与全血相似的感染受体的能力。引人注目的是，用多聚甲醛固定 WBC 不会影响在 tg338 中测量的感染性滴度，但会显著降低在绵羊中通过输血传播疾病的能力。这些结果表明，通过输血传播 TSE 可以非常高效，并且这种效率更依赖于输注细胞的活力，而不是通过 IC 接种测量的感染性水平。
