Pando-Robles Victoria, Oses-Prieto Juan A, Rodríguez-Gandarilla Myriam, Meneses-Romero Erika, Burlingame Alma L, Batista Cesar V F
Instituto Nacional de Salud Pública, Centro de Investigación Sobre Enfermedades Infecciosas (CISEI), Universidad No. 655 Colonia Santa María Ahuacatitlán, Cerrada Los Pinos y Caminera, C.P. 62100, Cuernavaca, Mor., México.
Department of Pharmaceutical Chemistry, University of California at San Francisco, 600 16th Street, 94158-2517, San Francisco, CA, USA.
J Proteomics. 2014 Dec 5;111:16-29. doi: 10.1016/j.jprot.2014.06.029. Epub 2014 Jul 5.
Dengue is an important and growing public health problem worldwide with an estimated 100million new clinical cases annually. Currently, no licensed drug or vaccine is available. During natural infection in humans, liver cells constitute one of the main targets of dengue virus (DENV) replication. However, a clear understanding of dengue pathogenesis remains elusive. In order to gain a better reading of the cross talk between virus and host cell proteins, we used a proteomics approach to analyze the host response to DENV infection in a hepatic cell line Huh-7. Differences in proteome expression were assayed 24h post-infection using label-free LC-MS. Quantitative analysis revealed 155 differentially expressed proteins, 64 of which were up-regulated and 91 down-regulated. These results reveal an important decrease in the expression of enzymes involved in the glycolytic pathway, citrate cycle, and pyruvate metabolism. This study provides large-scale quantitative information regarding protein expression in the early stages of infection that should be useful for better compression of the pathogenesis of dengue.
Dengue infection involves alterations in the homeostasis of the host cell. Defining the interactions between virus and cell proteins should provide a better understanding of how viruses propagate and cause disease. Here, we present for the first time the proteomic analysis of hepatocytes (Huh-7 cells) infected with DENV-2 by label-free LC-MS.
登革热是一个在全球范围内日益重要的公共卫生问题，估计每年有1亿新的临床病例。目前，尚无获得许可的药物或疫苗。在人类自然感染过程中，肝细胞是登革热病毒（DENV）复制的主要靶标之一。然而，对登革热发病机制的清晰理解仍然难以捉摸。为了更好地了解病毒与宿主细胞蛋白之间的相互作用，我们采用蛋白质组学方法分析了肝细胞系Huh-7对DENV感染的宿主反应。在感染后24小时使用无标记液相色谱-质谱法检测蛋白质组表达的差异。定量分析揭示了155种差异表达蛋白，其中64种上调，91种下调。这些结果表明参与糖酵解途径、柠檬酸循环和丙酮酸代谢的酶的表达有显著下降。本研究提供了关于感染早期蛋白质表达的大规模定量信息，这对于更好地理解登革热发病机制应该是有用的。
登革热感染涉及宿主细胞内稳态的改变。确定病毒与细胞蛋白之间的相互作用应该能更好地理解病毒如何传播和致病。在这里，我们首次通过无标记液相色谱-质谱法对感染DENV-2的肝细胞（Huh-7细胞）进行了蛋白质组学分析。
