Viral entry inhibitors block dengue antibody-dependent enhancement in vitro
Viral entry inhibitors block dengue antibody-dependent enhancement in vitro
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DOI：
10.1016/j.antiviral.2010.11.008
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发表时间：
2011-01-01
影响因子：
7.6
通讯作者：
Michael, Scott F.
中科院分区：
文献类型：
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作者：
Nicholson, Cindo O.;Costin, Joshua M.;Michael, Scott F.
严重的登革病毒(DENV)疾病症状，包括登革出血热和登革休克综合征，与先前存在的抗体的存在有关，这些抗体增强而不是中和Fc受体携带细胞的感染。这些抗体可能源于以前感染了不同血清型的登革热，或者来自婴幼儿断奶时出现的抗体滴度下降，母乳中含有保护性登革热特异性抗体。尽管这种抗体依赖增强(ADE)效应很重要，但目前还没有对这一过程的任何特定抑制剂的描述。我们探索了DENV进入抑制剂作为一种潜在的阻断ADE的策略。测试了两种不同的多肽进入抑制剂对抗体介导的人DENV-2感染的阻断能力。携带FcRII的K562细胞的体外实验。这两种多肽都能抑制ADE，表明进入抑制剂可能是开发针对严重DENV感染的特异性治疗方法的候选药物。(C)2010年爱思唯尔BM。版权所有。
Severe dengue virus (DENV) disease symptoms, including dengue hemorrhagic fever and dengue shock syndrome, have been correlated with the presence of pre-existing antibodies that enhance rather than neutralize infections in Fc receptor bearing cells. These antibodies can originate from previous infection with a different serotype of dengue, or from waning antibody titers that occur in infants and young children as they are weaned from breast milk that contains protective dengue-specific antibodies. Despite the apparent importance of this antibody dependent enhancement (ADE) effect, there has been no description of any specific inhibitors of this process. We explored DENV entry inhibitors as a potential strategy to block ADE. Two different peptide entry inhibitors were tested for the ability to block antibody-mediated DENV-2 infection of human. FcRII bearing K562 cells in vitro. Both peptides were able to inhibit ADE, showing that entry inhibitors are possible candidates for the development of specific treatment for severe DENV infection. (C) 2010 Elsevier BM. All rights reserved.