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Experimental Transmission of the Chronic Wasting Disease Agent to Swine after Oral or Intracranial Inoculation
Journal of Virology ( IF 5.4 ) Pub Date : 2017-10-01 , DOI: 10.1128/jvi.00926-17
S. Jo Moore 1, 2 , M. Heather West Greenlee 3 , Naveen Kondru 3 , Sireesha Manne 3 , Jodi D. Smith 1 , Robert A. Kunkle 1 , Anumantha Kanthasamy 3 , Justin J. Greenlee 1
Affiliation  

Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative disease of cervids. The potential for swine to serve as hosts for the agent of CWD is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Crossbred piglets were assigned to three groups, intracranially inoculated (n = 20), orally inoculated (n = 19), and noninoculated (n = 9). At approximately the age at which commercial pigs reach market weight, half of the pigs in each group were culled (“market weight” groups). The remaining pigs (“aged” groups) were allowed to incubate for up to 73 months postinoculation (mpi). Tissues collected at necropsy were examined for disease-associated prion protein (PrPSc) by Western blotting (WB), antigen capture enzyme immunoassay (EIA), immunohistochemistry (IHC), and in vitro real-time quaking-induced conversion (RT-QuIC). Brain samples from selected pigs were also bioassayed in mice expressing porcine prion protein. Four intracranially inoculated aged pigs and one orally inoculated aged pig were positive by EIA, IHC, and/or WB. By RT-QuIC, PrPSc was detected in lymphoid and/or brain tissue from one or more pigs in each inoculated group. The bioassay was positive in four out of five pigs assayed. This study demonstrates that pigs can support low-level amplification of CWD prions, although the species barrier to CWD infection is relatively high. However, detection of infectivity in orally inoculated pigs with a mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity.

IMPORTANCE We challenged domestic swine with the chronic wasting disease agent by inoculation directly into the brain (intracranially) or by oral gavage (orally). Disease-associated prion protein (PrPSc) was detected in brain and lymphoid tissues from intracranially and orally inoculated pigs as early as 8 months of age (6 months postinoculation). Only one pig developed clinical neurologic signs suggestive of prion disease. The amount of PrPSc in the brains and lymphoid tissues of positive pigs was small, especially in orally inoculated pigs. Regardless, positive results obtained with orally inoculated pigs suggest that it may be possible for swine to serve as a reservoir for prion disease under natural conditions.



中文翻译:

口服或颅内接种后慢性浪费性疾病病原体向猪的实验传播

慢性消耗性疾病(CWD)是一种自然发生的致命的宫颈变性神经退行性疾病。猪作为CWD病原体宿主的潜力尚不清楚。本研究的目的是研究实验性口服或颅内接种后猪对CWD剂的敏感性。杂种仔猪分为三组,分别是颅内接种(n = 20),口服接种(n = 19)和未接种(n= 9)。在大约商业猪达到市场体重的年龄时,每组一半的猪被淘汰(“市场体重”组)。其余的猪(“成年”组)可以在接种后(mpi)孵育长达73个月。尸检时收集的组织通过蛋白质印迹法(WB),抗原捕获酶免疫测定(EIA),免疫组织化学(IHC)和体外实时地震诱导的转化(RT-QuIC )检查疾病相关的ion病毒蛋白(PrP Sc)。)。还对表达猪蛋白的小鼠进行了生物测定。EIA,IHC和/或WB对4头颅内接种的成年猪和1头口服接种的成年猪呈阳性。由RT-QuIC,PrP Sc在每个接种组的一头或多头猪的淋巴样和/或脑组织中检测到了“幽门螺杆菌”。在五分之五的猪中,生物测定呈阳性。这项研究表明,尽管对CWD感染的物种障碍相对较高,但猪可以支持CWD ions病毒的低水平扩增。但是,用小鼠生物测定法检测经口接种的猪中的感染性增加了自然暴露的猪可以充当CWD感染性库的可能性。

重要我们通过慢性消瘦病原菌向家猪发起挑战,方法是直接接种到颅内(颅内)或通过管饲法(口服)。早在8个月大时(接种后6个月),在颅内和口服接种的猪的脑和淋巴组织中就检测到了与疾病相关的病毒蛋白(PrP Sc)。仅一头猪出现暗示neuro病毒疾病的临床神经系统体征。阳性猪的大脑和淋巴组织中的PrP Sc含量很小,尤其是在口服接种的猪中。无论如何,通过口服接种的猪获得的阳性结果表明,在自然条件下,猪可能会成为病毒疾病的宿主。

更新日期:2017-09-13
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