Zhang Qinyi, Yu Sicong, Yang Zhangnv, Wang Xingxing, Li Jianhua, Su Lingxuan, Zhang Huijun, Lou Xiuyu, Mao Haiyan, Sun Yi, Fang Lei, Yan Hao, Zhang Yanjun
Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, China.
School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Biomedicines. 2024 Nov 30;12(12):2752. doi: 10.3390/biomedicines12122752.
Dengue virus (DENV) is the most widespread mosquito-borne virus, which can cause dengue fever with mild symptoms, or progress to fatal dengue hemorrhagic fever and dengue shock syndrome. As the main target cells of DENV, macrophages are responsible for the innate immune response against the virus.
In this study, we investigated the role of pyroptosis in the pathogenic mechanism of dengue fever by examining the level of pyroptosis in DENV-1-infected macrophages and further screened differentially expressed microRNAs by high-throughput sequencing to predict microRNAs that could affect the pyroptosis of the macrophage.
Macrophages infected with DENV-1 were induced with decreased cell viability, decreased release of lactate dehydrogenase and IL-1β, activation of NLRP3 inflammasome and caspase-1, cleavage of GSDMD to produce an N-terminal fragment bound to cell membrane, and finally induced macrophage pyroptosis. MicroRNA expression profiles were obtained by sequencing macrophages from all periods of DENV-1 infection and comparing with the negative control. Sixty-three microRNAs differentially expressed in both the early and later stages of infection were also identified. In particular, miR-223-3p, miR-148a-3p, miR-125a-5p, miR-146a-5p and miR-34a-5p were recognized as small molecules that may be involved in the regulation of inflammation.
In summary, this study aimed to understand the pathogenic mechanism of DENV through relevant molecular mechanisms and provide new targets for dengue-specific therapy.
登革病毒（DENV）是传播最广泛的蚊媒病毒，可引起症状较轻的登革热，或发展为致命的登革出血热和登革休克综合征。巨噬细胞作为DENV的主要靶细胞，负责针对该病毒的固有免疫反应。
在本研究中，我们通过检测DENV-1感染的巨噬细胞中的细胞焦亡水平，研究细胞焦亡在登革热致病机制中的作用，并通过高通量测序进一步筛选差异表达的微小RNA，以预测可能影响巨噬细胞焦亡的微小RNA。
感染DENV-1的巨噬细胞出现细胞活力下降、乳酸脱氢酶和IL-1β释放减少、NLRP3炎性小体和半胱天冬酶-1激活、GSDMD裂解产生与细胞膜结合的N端片段，最终诱导巨噬细胞焦亡。通过对DENV-1感染各阶段的巨噬细胞进行测序并与阴性对照比较，获得了微小RNA表达谱。还鉴定出63种在感染早期和晚期均差异表达的微小RNA。特别是，miR-223-3p、miR-148a-3p、miR-125a-5p、miR-146a-5p和miR-34a-5p被认为是可能参与炎症调节的小分子。
总之，本研究旨在通过相关分子机制了解DENV的致病机制，并为登革热特异性治疗提供新的靶点。
