Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
In Vivo. 2020 Nov-Dec;34(6):3301-3308. doi: 10.21873/invivo.12168.
BACKGROUND/AIM: Hepatitis A virus (HAV) infection is still one of the serious health problems worldwide, despite the existence of effective vaccines for HAV. Zinc compounds have antiviral activities against various DNA and RNA viruses. Therefore, we investigated the effects of zinc compounds on the antiviral activity of interferon against HAV.
The effects of zinc compounds with or without interferon on HAV genotype IIIA HA11-1299 replication were examined in human hepatoma Huh7 cells. Cell viability was examined by the MTS assay. Inflammasome associated gene expression was examined by real-time reverse transcription-polymerase chain reaction.
Both zinc sulfate and zinc chloride had an inhibitory effect on HAV replication. Zinc sulfate tended to enhance while zinc chloride significantly enhanced the anti-HAV effect induced by interferon-alpha-2a. Zinc chloride significantly up-regulated mitogen-activated protein kinase 12 (MAPK12) and down-regulated 6 related genes [baculoviral IAP repeat containing 3 (BIRC3), interleukin 1 beta (IL1B), proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), prostaglandin-endoperoxide synthase 2 (PTGS2), PYD and CARD domain containing (PYCARD), and tumor necrosis factor (TNF)].
Zinc chloride inhibits HAV replication and has additive effects on the anti-HAV activities of interferon.
背景/目的:尽管存在针对甲型肝炎病毒(HAV)的有效疫苗,但 HAV 感染仍是全球严重的健康问题之一。锌化合物对多种 DNA 和 RNA 病毒具有抗病毒活性。因此,我们研究了锌化合物对干扰素抗 HAV 活性的影响。
在人肝癌细胞 Huh7 中,检测锌化合物与干扰素联合或不联合对 HAV 基因型 IIIA HA11-1299 复制的影响。通过 MTS 检测法检测细胞活力。通过实时逆转录-聚合酶链反应检测炎症小体相关基因的表达。
硫酸锌和氯化锌均对 HAV 复制具有抑制作用。硫酸锌有增强干扰素-α-2a 抗 HAV 作用的趋势,而氯化锌则显著增强。氯化锌显著上调丝裂原活化蛋白激酶 12(MAPK12)并下调 6 个相关基因[杆状病毒 IAP 重复序列包含 3(BIRC3)、白细胞介素 1β(IL1B)、脯氨酸-丝氨酸-苏氨酸磷酸酶相互作用蛋白 1(PSTPIP1)、前列腺素内过氧化物合酶 2(PTGS2)、PYD 和 CARD 结构域包含蛋白(PYCARD)和肿瘤坏死因子(TNF)]。
氯化锌抑制 HAV 复制,并与干扰素的抗 HAV 活性具有相加作用。