Study of CWD Deer and Elk Prion Disease in Nonhuman Primates

非人类灵长类动物 CWD 鹿和麋鹿朊病毒病的研究

• 批准号: 8156987
• 负责人: Bruce Chesebro
• 金额: $ 167.92万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8156987
• 关键词: Deer; Prion Diseases; nonhuman primate

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.

为了研究 CWD 跨物种传播的可能性，两种非人类灵长类动物（松鼠猴和食蟹猴）通过口腔或脑内感染来自 CWD 感染的鹿或麋鹿的大脑材料。 截至 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，并通过脑部生化和病理学检测证实患有朊病毒病。八只经口感染的松鼠猴也出现了疾病，其中三只仍无症状。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（所有猕猴均在 > 7 年前接种）。对剩余猴子的观察将继续进行。 2008 财年期间，另外四只食蟹猴和松鼠猴被接种了来自感染 CWD 的松鼠猴的脑匀浆，以评估 CWD 适应非人类灵长类宿主的能力。 2010 财年期间，两只接种了适应 CWD 的松鼠猴的松鼠猴均出现了疾病。 该接种物的潜伏期要快得多，临床症状略有不同，表明对新宿主或更高滴度的接种物的适应。 来自松鼠猴的 CWD 成功传代到其他松鼠猴体内，证实了朊病毒感染性的存在。这一确认很重要，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​​。 没有向“人源化”小鼠传播是令人鼓舞的数据，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外，我们还评估受感染松鼠猴的血液中是否存在朊病毒感染性。截至 2010 财年末，这些猴子均未表现出任何疾病迹象。