Study of CWD Deer and Elk Prion Disease in Nonhuman Primates

为了研究CWD跨物种传播的可能性，用感染CWD的鹿或麋鹿的脑组织材料经口或脑内感染两种非人类灵长类动物松猴和食蟹猴。在2010财年结束时，13只脑内感染的松鼠猴中有13只出现了临床神经症状，并经脑部生化和病理检查证实患有普恩病毒病。八只口服感染的松鼠猴也患上了疾病，其中三只仍然没有症状。到目前为止，无论接种途径如何，食蟹猴都没有出现任何疾病迹象(所有猕猴都是在7年前接种的)。对其余猴子的观察将继续进行。 在2008财年，另外四只食蟹猴和松鼠猴被接种了从感染CWD的松鼠猴脑匀浆中提取的脑匀浆，以评估CWD适应非人类灵长类宿主的能力。在2010财年期间，接种适应CWD的松鼠猴的两只松鼠猴都发生了疾病。这种接种剂的潜伏期要快得多，临床症状略有不同，表明适应了新的宿主或更高滴度的接种剂。从一只松鼠猴衍生的CWD成功地传给了另一只松鼠猴，证实了普恩病毒的存在。这一确认很重要，因为相同的松鼠猴CWD疫苗不会在表达人或鹿普恩蛋白的转基因小鼠中致病。缺乏对“人源化”小鼠的传播是令人鼓舞的数据，这些数据支持CWD可能不会感染人类的结论。 除了测试受感染的松鼠猴子的大脑外，我们还在评估受感染的松鼠猴子的血液中是否存在普恩病毒。在2010财年结束时，这些猴子中没有一只表现出任何疾病迹象。

To study the possibility of cross-species transmission of CWD, two species of nonhuman primates, squirrel monkeys and cynomologus macaques, were infected orally or intracerebrally with brain material derived from CWD affected deer or elk. At the conclusion of FY10 thirteen of thirteen intracerebrally infected squirrel monkeys had developed clinical neurological signs and were confirmed by biochemical and pathological testing of brain to have a prion disease. Eight orally infected squirrel monkeys have also developed disease, three remain asymptomatic. To this point no cynomologus macaques have developed any signs of disease regardless of inoculation route (all macaques were inoculated > 7 years ago). Observations on the remaining monkeys will continue. During FY08 four additional cynomologus macaques and squirrel monkeys were inoculated with brain homogenates derived from a CWD infected squirrel monkey to evaluate the ability of CWD to adapt to a nonhuman primate host. During FY10 both squirrel monkeys inoculated with squirrel monkey adapted CWD developed disease. The incubation period from this inocula was much faster and clinical signs were slightly different suggesting adaptation to a new host or a higher titer of inocula. The successful passage of CWD derived from a squirrel monkey into additional squirrel monkeys confirms the presence of prion infectivity. This confirmation was important since the same squirrel monkey CWD inocula did not cause disease in transgenic mice expressing human or deer prion protein. The lack of transmission to the "humanized" mice is encouraging data that supports the conclusion that CWD will likely not infect humans. In addition to testing infected squirrel monkey brain we are also evaluating blood from infected squirrel monkeys for the presence of prion infectivity. None of these monkeys have shown any signs of disease at the close of FY10.