Secretion of flaviviral non-structural protein NS1: from diagnosis to pathogenesis.
Secretion of flaviviral non-structural protein NS1: from diagnosis to pathogenesis.
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DOI：
10.1002/0470058005.ch17
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发表时间：
2006-01-01
影响因子：
--
通讯作者：
Flamand, M
中科院分区：
文献类型：
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作者：
Alcon-LePoder, S;Sivard, P;Flamand, M
黄病毒是主要的节肢动物传播的人类病原体，可导致危及生命的脑炎、肝炎和出血热。这些有包膜、单链、正义 RNA 病毒编码约 3400 个氨基酸的多蛋白前体，加工成 3 个结构蛋白和 7 个非结构蛋白。非结构糖蛋白 NS1 对于黄病毒的生存能力至关重要。在体外宿主细胞感染过程中，NS1 被发现与细胞内细胞器相关，是其在病毒复制中发挥作用的必要条件，或者被转运到细胞表面，在那里它可能触发特定的信号传导途径。此外，黄病毒感染的哺乳动物细胞会释放出分泌形式的蛋白质。我们之前已经表明，NS1 蛋白在疾病急性期在感染 1 型登革热病毒的患者血浆中循环，并将我们的回顾性研究扩展到 2 型和 3 型登革热队列，证实了 NS1 抗原作为替代诊断标记物的价值。有趣的是，在黄热病病毒和西尼罗河病毒感染中检测到 NS1 蛋白表明 NS1 分泌是人类黄病毒感染的标志。我们当前研究的目的是确定 NS1 蛋白分泌形式的生物学特性，评估其对病毒发病机制的可能贡献，并验证该蛋白作为黄病毒被动免疫预防的候选靶点。
Flaviviruses are major arthropod-borne human pathogens responsible for life-threatening encephalitis, hepatitis and haemorrhagic fevers. These enveloped, single-stranded, positive-sense RNA viruses encode a polyprotein precursor of about 3400 amino acids, processed into three structural and seven non-structural proteins. The non-structural glycoprotein NS1 is essential for flavivirus viability. During host-cell infection in vitro, NS1 is found associated with intracellular organelles as a requisite for its role in viral replication, or is transported to the cell surface where it may trigger specific signalling pathways. In addition, a secreted form of the protein is released from flavivirus-infected mammalian cells. We have previously shown that the NS1 protein circulates during the acute phase of the disease in the plasma of patients infected with dengue virus type 1 and have extended our retrospective studies to dengue type 2 and type 3 cohorts, confirming the value of the NS1 antigen as an alternative diagnostic marker. Interestingly, detection of the NS1 protein in yellow fever virus and West Nile virus infections suggests that NS1 secretion is a hallmark of human flavivirus infections. The objectives of our current studies are to define the biological properties of the secreted form of the NS1 protein, to evaluate its possible contribution to viral pathogenesis, and to validate this protein as a candidate target for passive immunoprophylaxis against flaviviruses.