Department of Molecular Biology, Indian Council of Medical Research (ICMR)-Vector Control Research Center - Field Station, Madurai, India.
Department of Biotechnology - Bioinformatics Infrastructure Facilities (DBT-BIF) Centre (Under DBT Biotechnology Information System Network (BTISNet) Scheme), Lady Doak College, Madurai, India.
Front Cell Infect Microbiol. 2021 Aug 10;11:681937. doi: 10.3389/fcimb.2021.681937. eCollection 2021.
Dengue virus (DENV) infection is prevalent in tropical and subtropical regions of the world, which is fatal if untreated symptomatically. Emergence of new genotype within serotypes led to enhanced severity. The objective of the study is to identify the molecular characteristics of the DENV circulated during 2017 outbreak in Tamil Nadu, India, and to investigate the role of inflammatory cytokines in different "serotypes" and in "dengue severity". A total of 135 suspected samples were tested for DENV infection using IgM, IgG, and qPCR assay; where 76 samples were positive for DENV and analyzed for 12 inflammatory cytokines using ELISA. Serotyping shows 14 DENV-1, 22 DENV-2, 7 DENV-3, and 33 DENV-4, where DENV-4 was predominant. Among 76, 42 isolates were successfully sequenced for C-prM region and grouped. A lineage shift was observed in DENV-4 genotype. Irrespective of serotypes, IFNγ was significantly elevated in all serotypes than control as well as in primary infection than secondary, indicating its role in immune response. GM-CSF and IP-10 were significantly elevated in secondary infection and could be used as prognostic biomarkers for secondary infection. Our observation shows differential cytokine expression profile varied with each serotype, indicating serotype/genotype-specific viral proteins might play a major role in dengue severity. DENV-4 as dominant serotype was reported in Tamil Nadu for the first time during an outbreak with a mixed Th1/Th17 cytokine expression profile that correlated with disease severity. We conclude it is essential to identify circulating viral genotype and their fitness by mutational analysis to correlate with disease severity and immune status, as this correlation will be helpful in diagnostics and therapeutics applications.
登革热病毒（DENV）感染在世界热带和亚热带地区流行，如果不进行症状治疗，可能会致命。血清型内新基因型的出现导致了严重程度的增加。本研究的目的是鉴定 2017 年在印度泰米尔纳德邦爆发期间传播的 DENV 的分子特征，并研究炎症细胞因子在不同“血清型”和“登革热严重程度”中的作用。使用 IgM、IgG 和 qPCR 检测共检测了 135 份疑似样本的 DENV 感染；其中 76 份样本呈 DENV 阳性，并使用 ELISA 检测了 12 种炎症细胞因子。血清分型显示有 14 株 DENV-1、22 株 DENV-2、7 株 DENV-3 和 33 株 DENV-4，其中 DENV-4 占优势。在 76 例中，成功对 C-prM 区进行了 42 个分离株测序并进行了分组。观察到 DENV-4 基因型的谱系转变。无论血清型如何，所有血清型中的 IFNγ 水平均显著高于对照组和原发性感染中的 IFNγ 水平，表明其在免疫反应中的作用。GM-CSF 和 IP-10 在二次感染中显著升高，可作为二次感染的预后生物标志物。我们的观察结果表明，不同的细胞因子表达谱因血清型而异，表明血清型/基因型特异性病毒蛋白可能在登革热严重程度中起主要作用。DENV-4 作为优势血清型在泰米尔纳德邦首次报道，在一次爆发中表现出 Th1/Th17 细胞因子表达谱，与疾病严重程度相关。我们的结论是，通过突变分析识别循环病毒基因型及其适应性以与疾病严重程度和免疫状态相关联是至关重要的，因为这种相关性将有助于诊断和治疗应用。
