Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
Institute for Human Infections & Immunity and Sealy & Smith Foundation, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
Viruses. 2023 Jul 21;15(7):1590. doi: 10.3390/v15071590.
Ebola virus (EBOV) causes Ebola virus disease (EVD), which is characterized by hemorrhagic fever with high mortality rates in humans. EBOV sexual transmission has been a concern since the 2014-2016 outbreak in Africa, as persistent infection in the testis and transmission to women was demonstrated. The only study related to establishing an intravaginal small animal infection model was recently documented in IFNAR mice using wild-type and mouse-adapted EBOV (maEBOV), and resulted in 80% mortality, supporting epidemiological data. However, this route of transmission is still poorly understood in women, and the resulting EVD from it is understudied. Here, we contribute to this field of research by providing data from immunocompetent BALB/c mice. We demonstrate that progesterone priming increased the likelihood of maEBOV vaginal infection and of exhibiting the symptoms of disease and seroconversion. However, our data suggest subclinical infection, regardless of the infective dose. We conclude that maEBOV can infect BALB/c mice through vaginal inoculation, but that this route of infection causes significantly less disease compared to intraperitoneal injection at a similar dose, which is consistent with previous studies using other peripheral routes of inoculation in that animal model. Our data are inconsistent with the disease severity described in female patients, therefore suggesting that BALB/c mice are unsuitable for modeling typical EVD following vaginal challenge with maEBOV. Further studies are required to determine the mechanisms by which EVD is attenuated in BALB/c mice, using maEBOV via the vaginal route, as in our experimental set-up.
埃博拉病毒（EBOV）会引起埃博拉病毒病（EVD），其特征是人类出血性发热和高死亡率。自 2014-2016 年非洲疫情爆发以来，人们一直担心埃博拉病毒的性传播，因为已经证明睾丸内持续性感染并可传播给女性。最近，在 IFNAR 小鼠中使用野生型和适应于小鼠的埃博拉病毒（maEBOV）建立了阴道小动物感染模型的唯一相关研究显示，80%的死亡率支持了流行病学数据。然而，在女性中，这种传播途径仍未得到充分理解，而且由此导致的 EVD 也研究不足。在这里，我们通过提供免疫功能正常的 BALB/c 小鼠的数据来为该研究领域做出贡献。我们证明孕激素预激活增加了 maEBOV 阴道感染和表现出疾病症状以及血清转化的可能性。但是，无论感染剂量如何，我们的数据表明存在亚临床感染。我们得出结论，maEBOV 可以通过阴道接种感染 BALB/c 小鼠，但与类似剂量的腹腔内注射相比，这种感染途径引起的疾病明显减少，这与该动物模型中使用其他外周接种途径的先前研究一致。我们的数据与女性患者描述的疾病严重程度不一致，因此表明 BALB/c 小鼠不适合通过阴道接种 maEBOV 来模拟典型的 EVD。需要进一步研究以确定通过阴道途径用 maEBOV 在 BALB/c 小鼠中减弱 EVD 的机制，就像我们的实验设置一样。
