慢性消耗性疾病 (CWD) 是一种鹿科朊病毒疾病，具有未知的人畜共患潜力，可能对接触的人类构成风险。为了评估 CWD 感染人类神经组织的潜力，我们使用了具有 2 种不同朊病毒基因型的人类大脑类器官，其中一种此前已被认为与人畜共患朊病毒病的易感性有关。我们将两种基因型的类器官暴露于来自 3 个不同来源的高浓度 CWD 接种物 7 天，然后定期筛查感染，长达 180 天。在暴露于 CWD 的类器官中，没有明显的从头 CWD 传播或蛋白酶抗性形式的人朊病毒沉积。检测到原始接种物有一定的持久性，这与朊病毒基因敲除类器官中的情况相同，因此不能归因于人类朊病毒的繁殖。总体而言，CWD 在大脑类器官中的不成功传播支持了 CWD 朊病毒向人类传播的强大物种屏障。

Chronic wasting disease (CWD) is a cervid prion disease with unknown zoonotic potential that might pose a risk to humans who are exposed. To assess the potential of CWD to infect human neural tissue, we used human cerebral organoids with 2 different prion genotypes, 1 of which has previously been associated with susceptibility to zoonotic prion disease. We exposed organoids from both genotypes to high concentrations of CWD inocula from 3 different sources for 7 days, then screened for infection periodically for up to 180 days. No de novo CWD propagation or deposition of protease-resistant forms of human prions was evident in CWD-exposed organoids. Some persistence of the original inoculum was detected, which was equivalent in prion gene knockout organoids and thus not attributable to human prion propagation. Overall, the unsuccessful propagation of CWD in cerebral organoids supports a strong species barrier to transmission of CWD prions to humans.