Characterization of an air-liquid interface primary human vaginal epithelium to study Ebola virus infection and testing of antivirals.
Characterization of an air-liquid interface primary human vaginal epithelium to study Ebola virus infection and testing of antivirals.
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DOI：
10.1016/j.antiviral.2023.105551
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发表时间：
2023-03
影响因子：
7.6
通讯作者：
中科院分区：
文献类型：
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作者：
埃博拉病毒（EBOV）是经常致命的埃博拉病毒病（EVD）的病原体，其特征是人类和非人类灵长类动物的出血热。男性幸存者的性传播是 2015 年至 2021 年间多起疫情暴发的根源。然而，人们对这一途径仍然知之甚少，并且由此产生的埃博拉病毒病也没有得到充分研究。为了支持记录女性性传播的流行病学研究，并作为从以前使用单层阴道上皮细胞 (VK2/E6E7) 的过渡，我们首先确定了两种相似的人类阴道上皮气液界面模型（VEC 和 VLC Epivaginal™）的生物学相关性，然后表征了它们对 EBOV 和病毒引起的炎症的易感性。最后，我们评估了 VLC 中聚苯撑羧亚甲基 (PPCM) 杀菌剂的毒性，并重新评估了其抗病毒效果。正如预期的那样，VEC 和 VLC 模型都显示出分层，包括上皮结构下的固有层，类似于人类阴道上皮的全厚度。然而，我们无法使用树突状细胞 CD1a 和 CD11c 标记检测阴道上皮最相关模型 (VLC) 中的免疫细胞。与我们之前使用 VK2/E6E7 细胞系的工作一致，从两个原代人类细胞系统的顶端检测到感染性病毒，但仅在使用高感染剂量时才检测到，滴度在 7 天内保持在 103-4 pfu/ml 的恒定水平，表明感染性病毒持续脱落。此外，感染导致两种模型的上皮细胞破裂，从顶端浅层到固有层都发现了病毒抗原，表明病毒已完全渗透，并总体证实了人类阴道组织对埃博拉病毒的易感性。就像之前在 VK2/E6E7 细胞中看到的那样，VLC 感染也导致炎症标志物显着增加，包括 IL-6、IL-8 和 IP-10，表明阴道炎，这再次与非人类灵长类动物中观察到的组织病变一致。最后，在感染前进行 5 分钟的 PPCM 杀菌剂治疗，可以预防 VLC 中的病毒感染和病毒诱导的炎症反应。
Ebola virus (EBOV) is the causative agent of the often-fatal Ebola virus disease (EVD) characterized by hemorrhagic fever in humans and non-human primates. Sexual transmission from male survivors has been at the origin of multiple outbreak flare-ups between 2015 and 2021. However, this route is still poorly understood and the resulting EVD from it is also understudied. To support epidemiological studies documenting sexual transmission to women, and as a transition from previously using monolayer vaginal epithelial cells (VK2/E6E7), we first determined the biological relevance of two similar air-liquid interface models of the human vaginal epithelium (VEC and VLC Epivaginal™) and then characterized their susceptibility to EBOV and virus-induced inflammation. Finally, we evaluated toxicity of Polyphenylene Carboxymethylene (PPCM) microbicide in VLC and reassessed its antiviral effect. As expected, the VEC, but also VLC model showed stratified layers including a lamina propria under an epithelial structure similar to the full thickness of the human vaginal epithelium. However, we could not detect the immune cells featured in the most relevant model (VLC) of the vaginal epithelium using the dendritic cell CD1a and CD11c markers. Consistent with our previous work using the VK2/E6E7 cell line, infectious virus was detected from the apical side of both primary human cell systems, but only when using a high infective dose, with titers remaining at a constant level of 103–4 pfu/ml over 7 days suggesting lasting infectious virus shedding. In addition, infection caused disruption of the epithelium of both models and virus antigen was found from the apical superficial layers down to the lamina propria suggesting full virus penetration and overall confirming the susceptibility of the human vaginal tissue for EBOV. Just like previously seen in VK2/E6E7 cells, VLC infection also caused significant increase in inflammatory markers including IL-6, IL-8, and IP-10 suggesting vaginitis which is again consistent with tissue lesions seen in non-human primates. Finally, both virus infection and virus-induced inflammatory response in VLC could be prevented by a single 5-min PPCM microbicide treatment prior infection.
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组织学，免疫组织化学和原位杂交揭示了埃博拉病毒疾病豚鼠模型中忽略的埃博拉病毒靶组织。
影响因子：
4.6
作者：
Cooper TK;Huzella L;Johnson JC;Rojas O;Yellayi S;Sun MG;Bavari S;Bonilla A;Hart R;Jahrling PB;Kuhn JH;Zeng X
通讯作者：
Zeng X
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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作者：
Deen GF;Broutet N;Xu W;Knust B;Sesay FR;McDonald SLR;Ervin E;Marrinan JE;Gaillard P;Habib N;Liu H;Liu W;Thorson AE;Yamba F;Massaquoi TA;James F;Ariyarajah A;Ross C;Bernstein K;Coursier A;Klena J;Carino M;Wurie AH;Zhang Y;Dumbuya MS;Abad N;Idriss B;Wi T;Bennett SD;Davies T;Ebrahim FK;Meites E;Naidoo D;Smith SJ;Ongpin P;Malik T;Banerjee A;Erickson BR;Liu Y;Liu Y;Xu K;Brault A;Durski KN;Winter J;Sealy T;Nichol ST;Lamunu M;Bangura J;Landoulsi S;Jambai A;Morgan O;Wu G;Liang M;Su Q;Lan Y;Hao Y;Formenty P;Ströher U;Sahr F
通讯作者：
Sahr F
影响因子：
105.7
作者：
EMOND, RTD;EVANS, B;LLOYD, G
通讯作者：
LLOYD, G
影响因子：
3.8
作者：
Escaffre, Olivier;Borisevich, Viktoriya;Rockx, Barry
通讯作者：
Rockx, Barry
影响因子：
3.7
作者：
通讯作者：
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