Molecular backgrounds of transplacental Zika fever infection.

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H04341
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Nihon University
• Principal Investigator: HAYAKAWA Satoshi 日本大学, 医学部, 教授 (30238084)
• Co-Investigator(Kenkyū-buntansha): 相澤 志保子 日本大学, 医学部, 准教授 (30513858) ; 川名 敬 日本大学, 医学部, 教授 (60311627) ; 森岡 一朗 日本大学, 医学部, 教授 (80437467)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: ジカ熱 / 垂直感染 / 胎盤関門 / 歯周病 / 絨毛羊膜炎 / 血管内皮 / TGF-β / 慢性炎症

Outline of Final Research Achievements

Zika fever causes congenital disorders including microcephaly. However, not all pregnant women develop intrauterine infections. This fact suggests the presence of a placental barrier. Periodontal disease and chorioamnionitis are considered to be risks for vertical transmission but the mechanism is so far unknown. We infected various trophoblast cell lines with Zika virus and examined their susceptibility. Though the natural virus replication and release were limited, TGF-β strongly enhanced infectivity, with enhanced expression of Tyro3 and AXL (the receptor for ZIKV) as a possible mechanism. The increased susceptibility of the villi themselves, in addition to exposure to highly susceptible Hofbauer cells and vascular endothelial cells due to disruption of the villi structure in pathological conditions such as periodontal disease and chorioamnionitis, was assumed to be a factor increasing the risk of vertical infection.

Free Research Field

産婦人科学

Academic Significance and Societal Importance of the Research Achievements

胎盤はジカウイルスに感染するが複製は制御されている。言い換えると、胎盤にはウイルスが胎児に侵入しないような防御機構が存在する。従って、妊婦は感染を避けることは極めて重要であるが、感染したからといって過度に心配する必要はない。しかし歯周病や絨毛羊膜炎などの炎症でバリアが破綻すると子宮内感染を来す。我々は感受性増強にはTGF-βが重要であることを証明したが、このメカニズムは風疹やCOVID-19でも同様である。妊婦と妊娠を希望する女性は慢性炎症を避けることが重要といえる。