Serum predictors of susceptibility to infection with West Nile virus

West Nile virus (WNV) is a mosquito-borne RNA flavivirus which has caused more than 31,000 cases in the USA from 1999-2011 including 1,262 fatalities. WNV infections are typically asymptomatic, but some patients, especially the elderly and immunocompromised, may experience severe neurological disease and even death. Control of WNV infection by the immune system is multifactorial. We profiled antibody and cytokine responses from a stratified cohort of WNV subjects to define immune responses that contribute to disease severity. While antibody levels were not significantly different between asymptomatic and severely ill subjects in our cohort, subjects with severe infections had lower levels of serum IL-4. Further, we detected 158 genes that were differentially expressed by asymptomatic and severely infected cohorts and using cluster analysis correlated WNV susceptibility with IL-4 related gene expression pathways. Our results suggest an important contribution for IL4 in more severe responses to WNV. Differential gene expression by human PBMCs from asymptomatic and severe patients with WNV infection were generated by microarray.

西尼罗河病毒（West Nile Virus, WNV）是一种经蚊媒传播的RNA黄病毒，1999年至2011年间在美国已造成超31000例感染病例，其中1262例死亡。西尼罗河病毒感染通常无明显症状，但部分患者（尤其是老年人及免疫功能低下者）可能出现严重神经系统疾病，甚至死亡。机体免疫系统对西尼罗河病毒感染的调控是多因素过程。本研究针对分层纳入的西尼罗河病毒感染者队列，对其抗体与细胞因子应答特征进行了分析，以明确与疾病严重程度相关的免疫应答机制。尽管本队列中无症状感染者与重症感染者的抗体水平无显著差异，但重症感染者的血清白细胞介素4（Interleukin-4, IL-4）水平更低。此外，本研究鉴定出158个在无症状与重症感染者队列中存在差异表达的基因，并通过聚类分析将西尼罗河病毒易感性与IL-4相关基因表达通路相关联。本研究结果表明，IL-4在西尼罗河病毒感染的重症化应答中发挥重要作用。本研究通过微阵列（microarray）技术，获取了西尼罗河病毒感染的无症状患者与重症患者的人外周血单个核细胞（Peripheral Blood Mononuclear Cell, PBMC）的差异基因表达数据。