Ebola and Marburg viruses replicate in monocyte-derived dendritic cells without inducing the production of cytokines and full maturation
Ebola and Marburg viruses replicate in monocyte-derived dendritic cells without inducing the production of cytokines and full maturation
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DOI：
10.1086/379199
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发表时间：
2003-12-01
影响因子：
6.4
通讯作者：
Schmaljohn, A
中科院分区：
文献类型：
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作者：
Bosio, CM;Aman, MJ;Schmaljohn, A
埃博拉病毒（EBOV）和马尔堡病毒（MARV）引起快速进行性出血热，死亡率高，并且可能具有逃避免疫破坏的专门机制。我们推测免疫逃避可能是由于EBOV和MARV干扰树突状细胞（DC）的能力，树突状细胞连接先天性和适应性免疫应答。我们证明了EBOV和MARV在原代人DC中感染和复制，而不诱导细胞因子分泌。感染的DC培养物支持指数病毒生长而不释放干扰素（IFN）-α，并且如果用双链RNA处理则IFN-α产生受损。此外，EBOV和MARV损害了DC支持T细胞增殖的能力，并且感染的未成熟DC经历异常成熟。这些发现可以解释EBOV和MARV-DCs的深刻毒力被禁用，并且有效的早期宿主应答由于对效率较低的次级机制的必要依赖而延迟。
Ebola virus (EBOV) and Marburg virus (MARV) cause rapidly progressive hemorrhagic fever with high mortality and may possess specialized mechanisms to evade immune destruction. We postulated that immune evasion could be due to the ability of EBOV and MARV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. We demonstrate that EBOV and MARV infected and replicated in primary human DCs without inducing cytokine secretion. Infected DC cultures supported exponential viral growth without releasing interferon (IFN)-alpha and were impaired in IFN-alpha production if treated with double-stranded RNA. Moreover, EBOV and MARV impaired the ability of DCs to support T cell proliferation, and infected, immature DCs underwent an anomalous maturation. These findings may explain the profound virulence of EBOV and MARV-DCs are disabled, and an effective early host response is delayed by the necessary reliance on less-efficient secondary mechanisms.