Mahidol-Osaka Center for Infectious Diseases, Faculty of Tropical Medicine, Mahidol University, Ratchathewi, Bangkok, Thailand.
Infect Genet Evol. 2013 Jul;17:210-5. doi: 10.1016/j.meegid.2013.04.005. Epub 2013 Apr 10.
The chikungunya virus (CHIKV) is a mosquito-borne virus that has recently re-emerged in several countries. On infection, the first vertebrate cells to come into contact with CHIKV are skin cells; mosquitoes inoculate the virus together with salivary gland protein into host skin while probing and feeding on blood. However, there is little known about the susceptibility of human skin cells to CHIKV infection. To clarify this, we investigated the kinetics of CHIKV in the human keratinocyte cell line, HaCaT. CHIKV actively replicated in HaCaT cells, with virus titers in the supernatant increasing to 2.8 × 10(4) plaque-forming units (PFU) ml(-1) 24h post infection. CHIKV infection suppressed production of interleukin-8 (IL-8) in HaCaT cells. The function of IL-8 is to recruit immune cells to virus-infected sites, a process known as chemotaxis. Furthermore, we assessed the role of mosquito salivary gland protein in CHIKV infections by comparing the levels of CHIKV gene expression and chemokine production in HaCaT cells with and without salivary gland extract (SGE). SGE enhanced both the expression of the CHIKV gene and the suppression effect of CHIKV on IL-8 production. Our data suggest that the HaCaT cell line represents an effective tool for investigating the mechanism of CHIKV transmission and spread in skin cells. At the mosquito bite site, CHIKV works together with SGE to ensure the virus replicates in skin cells and escapes the host immune system by suppression of IL-8 production.
基孔肯雅病毒（CHIKV）是一种蚊媒病毒，最近在多个国家重新出现。感染后，首先与 CHIKV 接触的脊椎动物细胞是皮肤细胞；蚊子在探测和吸食血液时，将病毒与唾液腺蛋白一起接种到宿主皮肤中。然而，人们对人类皮肤细胞对 CHIKV 感染的敏感性知之甚少。为了阐明这一点，我们研究了 CHIKV 在人角质形成细胞系 HaCaT 中的动力学。CHIKV 在 HaCaT 细胞中积极复制，感染后 24 小时上清液中的病毒滴度增加到 2.8×10(4)噬菌斑形成单位（PFU）ml(-1)。CHIKV 感染抑制 HaCaT 细胞中白细胞介素-8（IL-8）的产生。IL-8 的作用是招募免疫细胞到病毒感染部位，这一过程称为趋化作用。此外，我们通过比较有和没有唾液腺提取物（SGE）的 HaCaT 细胞中 CHIKV 基因表达和趋化因子产生水平来评估 SGE 在 CHIKV 感染中的作用。SGE 增强了 CHIKV 基因的表达和 CHIKV 对 IL-8 产生的抑制作用。我们的数据表明，HaCaT 细胞系是研究 CHIKV 在皮肤细胞中传播和传播机制的有效工具。在蚊子叮咬部位，CHIKV 与 SGE 一起作用，确保病毒在皮肤细胞中复制，并通过抑制 IL-8 的产生来逃避宿主免疫系统。
