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印度流行的登革病毒部分前膜和包膜序列的系统进化分析。

Phylogenetic analysis of partial pre-membrane and envelope sequences of dengue viruses circulating in India.

机构信息

Dept. of Clinical Virology, Christian Medical College, Vellore 632004, Tamil Nadu, India.

Dept. of Clinical Virology, Christian Medical College, Vellore 632004, Tamil Nadu, India.

出版信息

Int J Infect Dis. 2019 Jul;84S:S44-S56. doi: 10.1016/j.ijid.2019.04.010. Epub 2019 Apr 17.

DOI:10.1016/j.ijid.2019.04.010
PMID:31002930
Abstract

OBJECTIVE

Phylogenetic characteristics of circulating Indian dengue viruses (DENV) were analysed using partial pre-membrane (PrM) and envelope (E) sequences. An immunodominant region was analysed for mutations, and alignment with common DENV PCR primers and probes was determined.

METHODS

Published Indian PrM and E DENV sequences were analysed with hitherto unpublished PrM sequences from this study site. Alignments of DENV were checked for mutations in an immunodominant region and against the commonly used PCR primers and probes.

RESULTS

All four serotypes of DENV circulate in India. Genotype (G) GIII and GI of DENV-1 co-circulated in the south with significant PrM mutations before and after 2012. DENV-2 American genotype was first reported after which the Cosmopolitan genotype co-circulated with it in the southwest. The Cosmopolitan strain has been the only DENV-2 genotype circulating, although an Asian American genotype was recently reported. Significant mutations were found in the E region of DENV-2 strains. DENV-3 strains were GIII across the country. DENV-4 GI from the south and west has now spread across India. No significant mutations were found for DENV-3 or DENV-4. Indian strains showed mutations in an immunodominant region of the E gene and in the regions targeted by commonly used PCR primers and probes.

CONCLUSIONS

The genetic variability of Indian DENV with co-circulation of multiple genotypes suggests that genotype surveillance is crucial to determining the composition of dengue vaccines and understanding their contribution to epidemiology, virus fitness and pathogenesis. Some mutations seen in an immunodominant region of the E gene may allow these viruses to evade host immune cells. The mutations in the regions targeted by commonly used primers and probes necessitate higher degeneracy.

摘要

目的

利用部分前膜(PrM)和包膜(E)序列分析循环印度登革热病毒(DENV)的系统发育特征。分析了一个免疫显性区域的突变,并确定了与常见 DENV PCR 引物和探针的序列比对。

方法

分析了已发表的印度 PrM 和 E DENV 序列以及本研究地点尚未发表的 PrM 序列。检查 DENV 的对齐情况,以确定免疫显性区域的突变情况,并与常用的 PCR 引物和探针进行对比。

结果

所有四种血清型的 DENV 在印度流行。DENV-1 的基因型(G)GIII 和 GI 在南部共同流行,在 2012 年前后存在显著的 PrM 突变。首次报道了 DENV-2 的美国基因型,此后,其与普遍流行的基因型共同在西南部流行。尽管最近报告了亚洲美国基因型,但一直只有 Cosmopolitan 菌株在循环。在 E 区发现了 DENV-2 株的显著突变。全国各地的 DENV-3 株均为 GIII。来自南部和西部的 DENV-4 GI 现已遍布印度。DENV-3 或 DENV-4 未发现显著突变。印度株在 E 基因的免疫显性区域和常用 PCR 引物和探针靶向的区域发生突变。

结论

印度 DENV 的遗传变异性与多种基因型的共同流行表明,基因型监测对于确定登革热疫苗的组成以及了解其对流行病学、病毒适应性和发病机制的贡献至关重要。E 基因免疫显性区域的某些突变可能使这些病毒逃避宿主免疫细胞。常用引物和探针靶向区域的突变需要更高的简并性。

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