DataSheet_1_Cytokine Profiles and Antibody Response Associated to Choclo Orthohantavirus Infection.pdf

BackgroundNew World Hantaviruses (NWHs) are the etiological agent underlying hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with high mortality rates in humans. In Panama, infections with Choclo Orthohantavirus (CHOV) cause a much milder illness characterized by higher seroprevalence and lower mortality rates. To date, the cytokine profiles and antibody responses associated with this milder form of HCPS have not been defined. Therefore, in this study, we examined immune serological profiles associated with CHOV infections.MethodsFor this retrospective study, sera from fifteen individuals with acute CHOV-induced HCPS, were analyzed alongside sera from fifteen convalescent phase individuals and thirty-three asymptomatic, CHOV-seropositive individuals. Cytokine profiles were analyzed by multiplex immunoassay. Antibody subclasses, binding, and neutralization against CHOV-glycoprotein (CHOV-GP) were evaluated by ELISA, and flow cytometry.ResultsHigh titers of IFNγ, IL-4, IL-8, and IL-10 serum cytokines were found in the acute individuals. Elevated IL-4 serum levels were found in convalescent and asymptomatic seropositive individuals. High titers of IgG1 subclass were observed across the three cohorts analyzed. Neutralizing antibody response against CHOV-GP was detectable in few acute individuals but was strong in both convalescent and asymptomatic seropositive individuals.ConclusionA Th1/Th2 cytokine signature is characteristic during acute mild HCPS caused by CHOV infection. High expression of Th2 and IL-8 cytokines are correlated with clinical parameters in acute mild HCPS. In addition, a strong IL-4 signature is associated with different cohorts, including asymptomatic individuals. Furthermore, asymptomatic individuals presented high titers of neutralizing antibodies.

背景：新世界汉坦病毒（NWHs）是汉坦病毒心肺综合征（HCPS）的致病因素，这是一种严重呼吸系统疾病，在人类中具有高死亡率。在巴拿马，Choclo Orthohantavirus（CHOV）感染引起的疾病症状明显较轻，其特征为较高的血清阳性率和较低的死亡率。迄今为止，与这种较轻型HCPS相关的细胞因子谱和抗体反应尚未得到明确界定。因此，在本研究中，我们考察了与CHOV感染相关的免疫血清学特征。方法：本研究为回顾性研究，分析了15例急性CHOV引起的HCPS患者的血清，以及15例恢复期患者和33例无症状CHOV血清阳性个体的血清。细胞因子谱通过多重免疫测定进行分析。通过ELISA和流式细胞术评估了CHOV-糖蛋白（CHOV-GP）的抗体亚类、结合和中和作用。结果：急性个体血清中检测到高滴度的IFNγ、IL-4、IL-8和IL-10细胞因子。恢复期和无症状血清阳性个体血清中IL-4水平升高。在分析的三组人群中观察到IgG1亚类的高滴度。在少数急性个体中可检测到针对CHOV-GP的中和抗体反应，但在恢复期和无症状血清阳性个体中这种反应强烈。结论：由CHOV感染引起的急性轻症HCPS的特征是Th1/Th2细胞因子标志。Th2和IL-8细胞因子的高表达与急性轻症HCPS的临床参数相关。此外，IL-4标志与不同群体相关，包括无症状个体。此外，无症状个体表现出高滴度的中和抗体。