The Susceptibility of BALB/c Mice to a Mouse-Adapted Ebola Virus Intravaginal Infection.

The Susceptibility of BALB/c Mice to a Mouse-Adapted Ebola Virus Intravaginal Infection.
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DOI:
10.3390/v15071590
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发表时间:
2023-07-21
期刊:
Viruses
影响因子:
--
通讯作者:
Freiberg AN
Freiberg AN
中科院分区:
其他
文献类型:
--
作者:
Escaffre O;Juelich TL;Smith JK;Zhang L;Bourne N;Freiberg AN

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埃博拉病毒(Ebola Virus,EBOV)引起埃博拉病毒病(Ebola Virus Disease,EVD),以出血热为特征,人类死亡率高。自2014-2016年非洲爆发EBOV以来,性传播一直是一个令人担忧的问题,因为有证据表明,EBOV在睾丸中持续感染,并向女性传播。唯一与建立小动物阴道内感染模型有关的研究是最近在IFNAR−/−小鼠中使用野生型和小鼠适应的EBOV(MAEBOV)进行的,并导致了80%的死亡率,这支持了流行病学数据。然而,这种传播途径在妇女中仍然知之甚少,由此产生的埃博拉病毒病也没有得到充分的研究。在这里,我们通过提供具有免疫能力的BALB/c小鼠的数据来为这一领域的研究做出贡献。我们证明孕酮注射增加了MAEBOV阴道感染和表现出疾病和血清转换症状的可能性。然而,我们的数据表明,无论感染剂量如何,都是亚临床感染。我们的结论是,MAEBOV可以通过阴道接种感染BALB/c小鼠,但与类似剂量的腹腔注射相比,这种感染途径引起的疾病明显较少,这与之前在该动物模型中使用其他外围接种途径的研究一致。我们的数据与在女性患者中描述的疾病严重程度不一致,因此表明BALB/c小鼠不适合用MAEBOV阴道攻击后建立典型的EVD模型。需要进一步的研究来确定通过阴道途径使用MAEBOV在BALB/c小鼠中减弱EVD的机制,就像我们的实验装置一样。
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.
DOI: 10.3390/microorganisms9010156
发表时间: 2021-01-12
期刊: Microorganisms
影响因子: 4.5
作者:
Keiser PT;Anantpadma M;Staples H;Carrion R;Davey RA
通讯作者: Davey RA
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期刊: Scientific reports
影响因子: 4.6
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DOI: 10.1056/nejmoa1511410
发表时间: 2017-10-12
期刊: The New England journal of medicine
影响因子: --
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通讯作者: Sahr F
DOI: 10.1016/s0166-3542(98)00055-2
发表时间: 1999-01-01
期刊: ANTIVIRAL RESEARCH
影响因子: 7.6
作者:
Bourne, N;Ireland, J;Bernstein, DI
通讯作者: Bernstein, DI
DOI: 10.1128/aac.01711-17
发表时间: 2018-02-01
影响因子: 4.9
作者:
Ekins, Sean;Lingerfelt, Mary A.;Madrid, Peter B.
通讯作者: Madrid, Peter B.