Smither Sophie J, Nelson Michelle, Eastaugh Lin, Nunez Alejandro, Salguero Francisco J, Lever Mark S
Microbiology Group, CBR Division, Defence Science and Technology Laboratory (Dstl), Salisbury.
Pathology Department, Veterinary Laboratories Agency-Weybridge, Addlestone.
J Infect Dis. 2015 Oct 1;212 Suppl 2:S336-45. doi: 10.1093/infdis/jiv371. Epub 2015 Jul 23.
Ebola virus (EBOV) causes a highly infectious and lethal hemorrhagic fever in primates with high fatality rates during outbreaks and EBOV may be exploited as a potential biothreat pathogen. There is therefore a need to develop and license appropriate medical countermeasures against this virus. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess vaccines or therapies against EBOV disease (EVD), initial susceptibility, lethality and pathogenesis studies were performed. Low doses of EBOV-Kikwit, between 4 and 27 times the 50% tissue culture infectious dose, were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to EVD between 6 and 8 days after challenge. Typical signs of EVD were observed. Pathogenesis studies revealed that virus was isolated from the lungs of animals beginning on day 3 after challenge and from the liver, spleen and blood beginning on day 5. The most striking features were observed in animals that succumbed to infection, including high viral titers in all organs, increased levels of liver function enzymes and blood clotting times, decreased levels of platelets, multifocal moderate to severe hepatitis, and perivascular edema.
埃博拉病毒(EBOV)可在灵长类动物中引发具有高度传染性和致命性的出血热,在疫情爆发期间致死率很高,EBOV可能被用作潜在的生物威胁病原体。因此,有必要研发并批准针对这种病毒的适当医学应对措施。为了确定普通狨猴(Callithrix jacchus)是否会是评估针对埃博拉病毒病(EVD)的疫苗或疗法的合适模型,开展了初始易感性、致死率和发病机制研究。低剂量的埃博拉病毒基奎特株(EBOV-Kikwit),为50%组织培养感染剂量的4至27倍,足以引发致死性、可重复性感染。动物在第5至6天开始发热,在感染后6至8天死于埃博拉病毒病之前一直持续高烧。观察到了埃博拉病毒病的典型症状。发病机制研究显示,在感染后第3天开始可从动物的肺部分离到病毒,在第5天开始可从肝脏、脾脏和血液中分离到病毒。在死于感染的动物中观察到了最显著的特征,包括所有器官中病毒滴度高、肝功能酶水平和血液凝固时间增加、血小板水平降低、多灶性中度至重度肝炎以及血管周围水肿。