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寨卡病毒感染人胎盘肥大细胞和 HMC-1 细胞系,并引发脱颗粒、细胞因子释放和超微结构改变。

Zika Virus Infects Human Placental Mast Cells and the HMC-1 Cell Line, and Triggers Degranulation, Cytokine Release and Ultrastructural Changes.

机构信息

Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20551-030, Brazil.

Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil.

出版信息

Cells. 2020 Apr 16;9(4):975. doi: 10.3390/cells9040975.

DOI:10.3390/cells9040975
PMID:32316163
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7227014/
Abstract

Zika virus (ZIKV) is an emergent arthropod-borne virus whose outbreak in Brazil has brought major public health problems. Infected individuals have different symptoms, including rash and pruritus, which can be relieved by the administration of antiallergics. In the case of pregnant women, ZIKV can cross the placenta and infect the fetus leading to congenital defects. We have identified that mast cells in the placentae of patients who had Zika during pregnancy can be infected. This led to our investigation on the possible role of mast cells during a ZIKV infection, using the HMC-1 cell line. We analyzed their permissiveness to infection, release of mediators and ultrastructural changes. Flow cytometry detection of ZIKV-NS1 expression 24 h post infection in 45.3% of cells showed that HMC-1 cells are permissive to ZIKV infection. Following infection, β-hexosaminidase was measured in the supernatant of the cells with a notable release at 30 min. In addition, an increase in TNF-α, IL-6, IL-10 and VEGF levels were measured at 6 h and 24 h post infection. Lastly, different intracellular changes were observed in an ultrastructural analysis of infected cells. Our findings suggest that mast cells may represent an important source of mediators that can activate other immune cell types during a ZIKV infection, which has the potential to be a major contributor in the spread of the virus in cases of vertical transmission.

摘要

寨卡病毒(ZIKV)是一种新兴的虫媒病毒,其在巴西的爆发带来了重大的公共卫生问题。受感染的个体有不同的症状,包括皮疹和瘙痒,可通过给予抗过敏药物来缓解。对于孕妇而言,寨卡病毒可穿过胎盘并感染胎儿,导致先天缺陷。我们已经确定,妊娠期间感染寨卡病毒的患者胎盘内的肥大细胞可被感染。这促使我们使用 HMC-1 细胞系,研究肥大细胞在寨卡病毒感染中的可能作用。我们分析了它们对感染的易感性、介质释放和超微结构变化。感染后 24 小时,通过流式细胞术检测到 HMC-1 细胞中 45.3%的细胞表达寨卡病毒 NS1,表明其对寨卡病毒感染具有易感性。感染后,在细胞上清液中测量到β-己糖胺酶有明显释放,这发生在 30 分钟时。此外,在感染后 6 小时和 24 小时测量到 TNF-α、IL-6、IL-10 和 VEGF 水平增加。最后,在感染细胞的超微结构分析中观察到不同的细胞内变化。我们的研究结果表明,肥大细胞可能代表一种重要的介质来源,可在寨卡病毒感染期间激活其他免疫细胞类型,这有可能成为垂直传播中病毒传播的主要贡献者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe2/7227014/2856360caa53/cells-09-00975-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe2/7227014/43f7d739b97e/cells-09-00975-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe2/7227014/d92a26d1eeb9/cells-09-00975-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe2/7227014/ca401a13f921/cells-09-00975-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe2/7227014/2856360caa53/cells-09-00975-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe2/7227014/43f7d739b97e/cells-09-00975-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe2/7227014/c48ca788ea9b/cells-09-00975-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe2/7227014/d92a26d1eeb9/cells-09-00975-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe2/7227014/ca401a13f921/cells-09-00975-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe2/7227014/2856360caa53/cells-09-00975-g005.jpg

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