Lineage shift in Indian strains of Dengue virus serotype-3 (Genotype III), evidenced by detection of lineage IV strains in clinical cases from Kerala

Anoop Manakkadan,Riaz Ismail Kunju,Easwaran Sreekumar,Raji Rajendran Prasanna,Iype Joseph,Lalitha Kailas

doi:10.1186/1743-422x-10-37

Anoop Manakkadan, Riaz Ismail Kunju + Show 4 more

Open Access

https://doi.org/10.1186/1743-422x-10-37

Copy DOI

Abstract

BackgroundLocal epidemiology of Dengue is defined by the genetic diversity of the circulating Dengue virus (DENV) strains. This important information is not available for the virus strains from most parts of the Indian subcontinent. The present study focused on the genetic diversity of the serotype 3 DENV strains (DENV-3) from India.ResultsA total of 22 DENV-3 strains identified by reverse-transcription PCR analysis of serum samples from 709 patients were studied. These samples were collected over a period of 4 years (2008–2011) from dengue fever suspected patients from Kerala, a dengue endemic state in South India. Comparison of a 1740bp nucleotide sequence of the viral Capsid-Pre-membrane-Envelope coding region of our strains and previously reported DENV-3 strains from India, South Asia and South America revealed non-synonymous substitutions that were genotype III-specific as well as sporadic. Evidence of positive selection was detected in the I81 amino acid residue of the envelope protein. Out of the 22 samples, three had I81A and 18 had I81V substitutions. In the phylogenetic analysis by maximum likelihood method the strains from Kerala clustered in two different lineages (lineage III and IV) within genotype III clade of DENV-3 strains. The ten strains that belonged to lineage IV had a signature amino acid substitution T219A in the envelope protein. Interestingly, all these strains were found to be closely related to a Singapore strain GU370053 isolated in 2007.ConclusionsOur study identifies for the first time the presence of lineage IV strains in the Indian subcontinent. Results indicate the possibility of a recent exotic introduction and also a shift from the existing lineage III strains to lineage IV. Lineage shifts in DENV-3 strains have been attributed to dramatic increase in disease severity in many parts of the world. Hence the present observation could be significant in terms of the clinical severity of future dengue cases in the region.

Highlights

Local epidemiology of Dengue is defined by the genetic diversity of the circulating Dengue virus (DENV) strains
There is an exponential increase in the cases of Dengue fever (DF) or its severe forms, Dengue hemorrhagic fever (DHF)/Dengue shock syndrome (DSS) across the
Viral nucleic acid and anti-dengue IgG detection In the four year period (2008–2011) of the study, acutephase serum samples from dengue-suspected patients were collected from different parts of Kerala (Figure 1)

Summary

Introduction

Local epidemiology of Dengue is defined by the genetic diversity of the circulating Dengue virus (DENV) strains. A mosquito vector transmitted viral infection, has emerged as a major disease in recent times [1,2]. The NS5 protein functions as the viral RNAdependent RNA polymerase that is responsible for replicating the genome [4] This protein has a low fidelity during the viral genome replication contributing to the genomic variability within the viral serotypes and a constantly changing epidemiology of dengue. Identifying such changes by genome analysis has become a major tool in understanding dengue disease dynamics [5]. Previous studies have reported that almost all gene segments of the virus are useful in generating information on the viral evolution [6,7], though whole genome analysis has gained more emphasis recently [8,9,10]

Methods

Results

Discussion

Conclusion