Department of Biomedical Sciences, Dstl, Porton Down, Salisbury, Wiltshire, UK.
Int J Exp Pathol. 2013 Apr;94(2):156-68. doi: 10.1111/iep.12018. Epub 2013 Feb 27.
Marburg virus causes a highly infectious and lethal haemorrhagic fever in primates and may be exploited as a potential biothreat pathogen. To combat the infection and threat of Marburg haemorrhagic fever, there is a need to develop and license appropriate medical countermeasures. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess therapies against Marburg haemorrhagic fever, initial susceptibility, lethality and pathogenesis studies were performed. Low doses of virus, between 4 and 28 TCID50 , were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to disease between 8 and 11 days postchallenge. Typical signs of Marburg virus infection were observed including haemorrhaging and a transient rash. In pathogenesis studies, virus was isolated from the animals' lungs from day 3 postchallenge and from the liver, spleen and blood from day 5 postchallenge. Early signs of histopathology were apparent in the kidney and liver from day 3. The most striking features were observed in animals exhibiting severe clinical signs, which included high viral titres in all organs, with the highest levels in the blood, increased levels in liver function enzymes and blood clotting times, decreased levels in platelets, multifocal moderate-to-severe hepatitis and perivascular oedema.
马尔堡病毒可导致灵长类动物发生高度传染性和致命性出血热,可能被用作潜在的生物威胁病原体。为了应对马尔堡出血热感染和威胁,有必要开发和授权适当的医疗对策。为了确定普通狨猴(Callithrix jacchus)是否是评估针对马尔堡出血热疗法的合适模型,进行了初始易感性、致死性和发病机制研究。低剂量的病毒(4 至 28TCID50)足以导致致命的、可重复的感染。动物在第 5 至 6 天出现发热,在第 8 至 11 天因疾病而死亡之前持续高热。观察到了马尔堡病毒感染的典型症状,包括出血和短暂皮疹。在发病机制研究中,从感染后第 3 天的动物肺部和第 5 天的肝脏、脾脏和血液中分离到了病毒。从第 3 天开始,肾脏和肝脏就出现了组织病理学早期迹象。在表现出严重临床症状的动物中观察到了最显著的特征,包括所有器官中的高病毒滴度,血液中的病毒滴度最高,肝功能酶和凝血时间升高,血小板减少,局灶性中重度肝炎和血管周围水肿。