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，两种非人灵长类动物，松鼠猴和食蟹猴，经口或脑内感染来自CWD受影响的鹿或麋鹿的脑材料。 在2011财政年度结束时，13只脑内感染的松鼠猴中有13只出现了临床神经系统症状，并通过脑生化和病理学检测证实患有朊病毒病。九只经口感染的松鼠猴也出现疾病，两只仍然没有症状。在FY11期间，两只受感染的食蟹猴因与典型朊病毒疾病体征无关的原因被安乐死，并进行朊病毒疾病检测。到目前为止，无论接种途径如何，没有食蟹猴发生朊病毒病（所有猕猴均在> 8年前接种）。将继续对其余猴进行观察。 在2008财年期间，另外4只食蟹猴和松鼠猴接种了来自CWD感染松鼠猴的脑匀浆，以评价CWD适应非人灵长类宿主的能力。在FY10期间，接种了适应性CWD的松鼠猴的两只松鼠猴均发生了疾病。 该接种物的潜伏期快得多，临床体征略有不同，表明适应了新的宿主或接种物的滴度更高。 来自松鼠猴的慢性消耗病成功传播到其他松鼠猴中证实了朊病毒感染性的存在。这一确认是重要的，因为相同的松鼠猴CWD接种物不会在表达人或鹿朊病毒蛋白的转基因小鼠中引起疾病。为了进一步测试CWD对人类嗜性的适应性，我们在FY11期间将临床患病的第二代松鼠猴的材料接种到表达人朊病毒蛋白的转基因小鼠中。 没有传播到“人源化”小鼠是令人鼓舞的数据，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大脑，我们还评估了受感染松鼠猴血液中朊病毒的感染性。在2011财年结束时，这些猴子中没有一只显示出任何疾病迹象。

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 FY11 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. Nine orally infected squirrel monkeys have also developed disease, two remain asymptomatic. During FY11 two infected cynomologus macaques were euthanized for reasons unrelated to typical prion disease signs and tested for prion disease. To this point no cynomologus macaques have developed prion disease regardless of inoculation route (all macaques were inoculated > 8 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. To further test adaptation of CWD to either a human tropism we have inoculated material from the clinically ill second passage squirrel monkeys into transgenic mice expressing human prion protein during FY11. 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 FY11.