Antibody neutralization and viral virulence in recurring dengue virus type 2 outbreaks

Antibody neutralization and viral virulence in recurring dengue virus type 2 outbreaks
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DOI:
10.1089/vim.2006.0100
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发表时间:
2007-09-01
期刊:
影响因子:
2.2
通讯作者:
Abubakar, Sazaly
Abubakar, Sazaly
中科院分区:
医学4区
文献类型:
--
作者:
Wong, Sook-San;Abd-Jamil, Juraina;Abubakar, Sazaly

文献摘要

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涉及相同基因型登革热病毒(DENV)的疫情在马来西亚周期性发生。20世纪90年代在马来西亚巴生谷发生了涉及相同基因型的2型登革热病毒(DENV-2)的两个暴发周期。第一次爆发的患者血清和同一次爆发的病毒接种小鼠血清对第二次爆发的病毒的中和活性较差。相反,第二次爆发的患者血清对早期爆发的病毒表现出更高的中和效价。在亚中和浓度下,用第二次爆发病毒免疫的小鼠血清对早期爆发的病毒感染没有显著增强。NS1包膜蛋白(E)第129位的缬氨酸替换为异亮氨酸,第117位的苏氨酸替换为丙氨酸,第272位的赖氨酸替换为精氨酸,这两种氨基酸的替换使病毒发生了分化。这些发现强调了特定的基因型内变异在引发针对不同DENV亚基因型的不同宿主免疫反应方面的潜在影响。这可能是在登革热流行地区反复出现同质型登革热病毒暴发的一个重要因素。
Outbreaks involving dengue viruses (DENV) of the same genotype occur in a cyclical pattern in Malaysia. Two cycles of outbreaks involving dengue virus type 2 (DENV-2) of the same genotype occurred in the 1990s in the Klang Valley, Malaysia. Sera of patients from the first outbreak and sera of mice inoculated with virus from the same outbreak had poorer neutralization activity against virus of the second outbreak. Conversely, patient sera from the second outbreak showed higher neutralization titer against virus of the early outbreak. At subneutralizing concentrations, sera of mice immunized with second outbreak virus did not significantly enhance infection with viruses from the earlier outbreak. Amino acid substitution from valine to isoleucine at position 129 of the envelope protein ( E), as well as threonine to alanine at position 117 and lysine to arginine at position 272 of the NS1 protein, differentiated viruses of the two outbreaks. These findings highlight the potential influence of specific intragenotypic variations in eliciting varied host immune responses against the different DENV subgenotypes. This could be an important contributing factor in the recurring homogenotypic dengue virus outbreaks seen in dengue-endemic regions.