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Emergence of Dengue 4 as Dominant Serotype During 2017 Outbreak in South India and Associated Cytokine Expression Profile.

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.

SUBMITTER: Gowri Sankar S

PROVIDER: S-EPMC8382982 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundInfection by dengue virus (DENV) is a major public health concern in hundreds of tropical and subtropical countries. French Polynesia (FP) regularly experiences epidemics that initiate, or are consecutive to, DENV circulation in other South Pacific Island Countries (SPICs). In January 2009, after a decade of serotype 1 (DENV-1) circulation, the first cases of DENV-4 infection were reported in FP. Two months later a new epidemic emerged, occurring about 20 years after the previous circulation of DENV-4 in FP. In this study, we investigated the epidemiological and molecular characteristics of the introduction, spread and genetic microevolution of DENV-4 in FP.Methodology/principal findingsEpidemiological data suggested that recent transmission of DENV-4 in FP started in the Leeward Islands and this serotype quickly displaced DENV-1 throughout FP. Phylogenetic analyses of the nucleotide sequences of the envelope (E) gene of 64 DENV-4 strains collected in FP in the 1980s and in 2009-2010, and some additional strains from other SPICs showed that DENV-4 strains from the SPICs were distributed into genotypes IIa and IIb. Recent FP strains were distributed into two clusters, each comprising viruses from other but distinct SPICs, suggesting that emergence of DENV-4 in FP in 2009 resulted from multiple introductions. Otherwise, we observed that almost all strains collected in the SPICs in the 1980s exhibit an amino acid (aa) substitution V287I within domain I of the E protein, and all recent South Pacific strains exhibit a T365I substitution within domain III.Conclusions/significanceThis study confirmed the cyclic re-emergence and displacement of DENV serotypes in FP. Otherwise, our results showed that specific aa substitutions on the E protein were present on all DENV-4 strains circulating in SPICs. These substitutions probably acquired and subsequently conserved could reflect a founder effect to be associated with epidemiological, geographical, eco-biological and social specificities in SPICs.

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Emergence of Dengue 4 as Dominant Serotype During 2017 Outbreak in South India and Associated Cytokine Expression Profile.

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