Abstract
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.
Highlights
IntroductionDengue is an endemic arbovirus disease, and ~3.9 billion peoples from more than 125 countries (accounting 40% of world population) are at risk (Bhatt et al, 2013)
Dengue is an endemic arbovirus disease, and ~3.9 billion peoples from more than 125 countries are at risk (Bhatt et al, 2013)
The dengue virus has four genetically distinct serotypes (DENV 1–4) that can cause either febrile flu-like symptoms, i.e., dengue fever (DF) or severe form called dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), which is characterized by vascular permeability and plasma leakage (Halstead and Cohen, 2015)
Summary
Dengue is an endemic arbovirus disease, and ~3.9 billion peoples from more than 125 countries (accounting 40% of world population) are at risk (Bhatt et al, 2013). Most studies focus on dengue severity (DF, DHF, DSS) or primary and secondary infection; fewer reports are available on comparative study of cytokine expression within serotypes [see (Sierra et al, 2012; Cruz Hernandez et al, 2016; Yang et al, 2016)]. We hypothesize that serotype variation might induce differential cytokine expression profile among primary and secondary and with respect to severity In this aspect, we undertook the study in the state of Tamil Nadu during the 2017 outbreak with the focus on (1) identifying molecular phylogeny of DENV circulation during the outbreak and (2) analyzing differential cytokine expression by serotypes (DENV 1–4) among primary and secondary infection, as well as in dengue severity (DF, DHF, and DSS)
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