Department of Internal Medicine, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo State, Brazil.
Department of Internal Medicine, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo State, Brazil.
Virus Res. 2018 Sep 2;256:166-173. doi: 10.1016/j.virusres.2018.08.011. Epub 2018 Aug 23.
Two Alphaviruses stand out for their clinical importance in Brazil: chikungunya (CHIKV) and mayaro (MAYV) viruses. Few studies exist on the mechanisms of the immune response after infection by these viruses and neither a treatment nor a vaccine for these pathogens are available. Although their infection does not have a high mortality rate, they can lead to a joint involvement that can persist for months. The aims of this work were the study of the mechanisms of antiviral immune response following in vitro (U937 cells) infection with these viruses; to investigate the characteristics of the infection by these viruses; and to determine possible molecular targets that could serve as antiviral therapies against these pathogens. Several genes were modulated after infection by these viruses, and the three antiviral detection and response pathways were activated (Toll-like, RIG-I and NOD-like). Eotaxin and IL-6 were induced in all experiments. The cellular immune response profile found for each virus was different, with CHIKV activating primarily an inflammatory response (Th1 and Th17) and MAYV inducing a regulatory/suppressive response, an important feature to contain the inflammation resulting from infection. The data acquired by this study could provide an explanation why CHIKV infections, due to activation of the inflammatory response, are more clinically relevant than MAYV infections, which generates mostly an anti-inflammatory response after infection.
在巴西,两种甲病毒因其在临床上的重要性而引人注目:基孔肯雅热病毒(CHIKV)和马亚罗病毒(MAYV)。关于这些病毒感染后免疫反应的机制的研究很少,也没有针对这些病原体的治疗方法或疫苗。虽然它们的感染死亡率不高,但它们会导致关节受累,这种情况可能会持续数月。本工作的目的是研究这些病毒体外(U937 细胞)感染后抗病毒免疫反应的机制;研究这些病毒感染的特征;并确定可能作为针对这些病原体的抗病毒治疗的潜在分子靶标。这些病毒感染后,有几个基因发生了调节,三种抗病毒检测和反应途径被激活(Toll 样受体、RIG-I 和 NOD 样受体)。在所有实验中均诱导了嗜酸性粒细胞趋化因子和白细胞介素 6。针对每种病毒发现的细胞免疫反应特征不同,CHIKV 主要激活炎症反应(Th1 和 Th17),而 MAYV 诱导调节/抑制反应,这是控制感染引起的炎症的重要特征。本研究获得的数据可以解释为什么 CHIKV 感染由于炎症反应的激活而比 MAYV 感染更具临床相关性,后者在感染后主要产生抗炎反应。