Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Pretoria 0002, South Africa.
Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
Viruses. 2021 Apr 20;13(4):709. doi: 10.3390/v13040709.
Rift Valley fever phlebovirus (RVFV) infects humans and a wide range of ungulates and historically has caused devastating epidemics in Africa and the Arabian Peninsula. Lesions of naturally infected cases of Rift Valley fever (RVF) have only been described in detail in sheep with a few reports concerning cattle and humans. The most frequently observed lesion in both ruminants and humans is randomly distributed necrosis, particularly in the liver. Lesions supportive of vascular endothelial injury are also present and include mild hydropericardium, hydrothorax and ascites; marked pulmonary congestion and oedema; lymph node congestion and oedema; and haemorrhages in many tissues. Although a complete understanding of RVF pathogenesis is still lacking, antigen-presenting cells in the skin are likely the early targets of the virus. Following suppression of type I IFN production and necrosis of dermal cells, RVFV spreads systemically, resulting in infection and necrosis of other cells in a variety of organs. Failure of both the innate and adaptive immune responses to control infection is exacerbated by apoptosis of lymphocytes. An excessive pro-inflammatory cytokine and chemokine response leads to microcirculatory dysfunction. Additionally, impairment of the coagulation system results in widespread haemorrhages. Fatal outcomes result from multiorgan failure, oedema in many organs (including the lungs and brain), hypotension, and circulatory shock. Here, we summarize current understanding of RVF cellular tropism as informed by lesions caused by natural infections. We specifically examine how extant knowledge informs current understanding regarding pathogenesis of the haemorrhagic fever form of RVF, identifying opportunities for future research.
裂谷热病毒（RVFV）感染人类和广泛的有蹄类动物，历史上曾在非洲和阿拉伯半岛引发毁灭性的流行病。裂谷热（RVF）自然感染病例的病变仅在绵羊中详细描述过，仅有少数关于牛和人类的报道。在反刍动物和人类中最常观察到的病变是随机分布的坏死，特别是在肝脏中。也存在支持血管内皮损伤的病变，包括轻度的心包积液、胸腔积液和腹水；明显的肺充血和水肿；淋巴结充血和水肿；以及许多组织中的出血。尽管对 RVF 发病机制的全面理解仍缺乏，但皮肤中的抗原呈递细胞可能是病毒的早期靶标。在抑制 I 型 IFN 产生和真皮细胞坏死后，RVFV 会全身扩散，导致各种器官中其他细胞的感染和坏死。先天和适应性免疫反应未能控制感染，淋巴细胞凋亡加剧。过度的促炎细胞因子和趋化因子反应导致微循环功能障碍。此外，凝血系统的损伤导致广泛的出血。多器官衰竭、许多器官（包括肺和脑）水肿、低血压和循环性休克导致致命后果。在这里，我们总结了目前对 RVF 细胞嗜性的理解，这些理解来自自然感染引起的病变。我们特别研究了现有的知识如何为 RVF 出血热形式的发病机制提供当前的理解，并确定了未来研究的机会。
