Macrophages as target cells for Mayaro virus infection: involvement of reactive oxygen species in the inflammatory response during virus replication
Macrophages as target cells for Mayaro virus infection: involvement of reactive oxygen species in the inflammatory response during virus replication
复制标题
DOI：
10.1590/0001-3765201620150685
复制
发表时间：
2016-09-01
期刊：
影响因子：
--
通讯作者：
POIAN, ANDREA T. DA
中科院分区：
文献类型：
--
作者：
CAVALHEIRO, MARIANA G.;COSTA, LEANDRO SILVA DA;POIAN, ANDREA T. DA
甲病毒是引起关节炎的病毒之一，通过引起局部爆发以及人类大规模流行病而构成全球公共卫生问题。有趣的是，虽然旧世界甲病毒是致关节炎的，但新世界甲病毒引起脑炎。一个例外是马亚罗病毒（MAYV），它只在南美洲传播，但会引起关节痛，并且与旧世界甲病毒有遗传学上的联系。虽然MAYV诱导的人类关节炎是有据可查的，分子和细胞因子，有助于其发病机制是完全未知的。在这项研究中，我们首次证明了巨噬细胞，关节炎发展中的关键角色，是MAYV感染的靶细胞，通过凋亡导致细胞死亡。我们发现MAYV在巨噬细胞中的复制诱导了TNF的表达，TNF是一种有助于MAYV发热发病机制的细胞因子，因为TNF促进了关节炎的炎症特征。我们还发现，在感染的早期，活性氧（ROS）的产生显着增加，这与病毒复制的高峰期相一致，并在TNF分泌之前。感染后立即用抗氧化剂处理细胞完全消除了TNF的分泌，表明活性氧参与了MAYV感染期间诱导的炎症。
Alphaviruses among the viruses that cause arthritis, consisting in a public health problem worldwide by causing localized outbreaks, as well as large epidemics in humans. Interestingly, while the Old World alphaviruses are arthritogenic, the New World alphaviruses cause encephalitis. One exception is Mayaro virus (MAYV), which circulates exclusively in South America but causes arthralgia and is phylogenetically related to the Old World alphaviruses. Although MAYV-induced arthritis in humans is well documented, the molecular and cellular factors that contribute to its pathogenesis are completely unknown. In this study, we demonstrated for the first time that macrophages, key players in arthritis development, are target cells for MAYV infection, which leads to cell death through apoptosis. We showed that MAYV replication in macrophage induced the expression of TNF, a cytokine that would contribute to pathogenesis of MAYV fever, since TNF promotes an inflammatory profile characteristic of arthritis. We also found a significant increase in the production of reactive oxygen species (ROS) at early times of infection, which coincides with the peak of virus replication and precedes TNF secretion. Treatment of the cells with antioxidant agents just after infection completely abolished TNF secretion, indicating an involvement of ROS in inflammation induced during MAYV infection.