Casseb Samir Mansour Moraes, Melo Karla Fabiane Lopes de, Carvalho Carlos Alberto Marques de, Santos Carolina Ramos Dos, Franco Edna Cristina Santos, Vasconcelos Pedro Fernando da Costa
Experimental Pathology Section, Evandro Chagas Institute, Ananindeua 67030-000, PA, Brazil.
Oncology Research Center, Federal University of Pará, Belém 66075-110, PA, Brazil.
Curr Issues Mol Biol. 2023 May 26;45(6):4589-4599. doi: 10.3390/cimb45060291.
The World Health Organization has estimated the annual occurrence of approximately 392 million dengue virus (DENV) infections in more than 100 countries where the virus is endemic, which represents a serious threat to humanity. DENV is a serologic group with four distinct serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) belonging to the genus , in the family . Dengue is the most widespread mosquito-borne disease in the world. The ~10.7 kb DENV genome encodes three structural proteins (capsid (C), pre-membrane (prM), and envelope (E)) and seven non-structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). The NS1 protein is a membrane-associated dimer and a secreted, lipid-associated hexamer. Dimeric NS1 is found on membranes both in cellular compartments and cell surfaces. Secreted NS1 (sNS1) is often present in patient serum at very high levels, which correlates with severe dengue symptoms. This study was conducted to discover how the NS1 protein, microRNAs-15/16 (miRNAs-15/16), and apoptosis are related during DENV-4 infection in human liver cell lines. Huh 7.5 and HepG2 cells were infected with DENV-4, and miRNAs-15/16, viral load, NS1 protein, and caspases-3/7 were quantified after different durations of infection. This study demonstrated that miRNAs-15/16 were overexpressed during the infection of HepG2 and Huh 7.5 cells with DENV-4 and had a relationship with NS1 protein expression, viral load, and the activity of caspases-3/7, thus making these miRNAs potential injury markers during DENV infection in human hepatocytes.
世界卫生组织估计，在登革热病毒（DENV）流行的100多个国家中，每年约有3.92亿例DENV感染病例，这对人类构成了严重威胁。DENV是一个血清学组，有四种不同的血清型（DENV-1、DENV-2、DENV-3和DENV-4），属于黄病毒属，黄病毒科。登革热是世界上传播最广泛的蚊媒疾病。约10.7 kb的DENV基因组编码三种结构蛋白（衣壳（C）、前膜（prM）和包膜（E））和七种非结构（NS）蛋白（NS1、NS2A、NS2B、NS3、NS4A、NS4B和NS5）。NS1蛋白是一种与膜相关的二聚体，也是一种分泌型、与脂质相关的六聚体。二聚体NS1存在于细胞区室的膜和细胞表面。分泌型NS1（sNS1）在患者血清中通常以非常高的水平存在，这与严重的登革热症状相关。本研究旨在探讨在人肝癌细胞系中DENV-4感染期间NS1蛋白、微小RNA-15/16（miRNAs-15/16）与细胞凋亡之间的关系。用DENV-4感染Huh 7.5和HepG2细胞，并在不同感染时间后对miRNAs-15/16、病毒载量、NS1蛋白和半胱天冬酶-3/7进行定量。本研究表明，在HepG2和Huh 7.5细胞被DENV-4感染期间，miRNAs-15/16表达上调，且与NS1蛋白表达、病毒载量及半胱天冬酶-3/7的活性有关，因此这些miRNAs可能是人肝细胞DENV感染期间的潜在损伤标志物。
