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

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.

Emergence of new genotypes and lineages of dengue viruses during the 2012–15 epidemics in southern India

“…However, majority of our sequences (23/32), diverged and clustered together to form a new lineage 'GIVc', exhibiting minimum nucleotide divergence of 3%-4% with the closest GIVb strains (Delhi-2003 andKerala-2010). In some of the previous Indian dengue outbreaks, emergence or shift of new lineages has been documented in other serotypes/genotypes such as; GIII of DENV-1 in 2006 outbreaks in Delhi (Kukreti et al, 2008) and GIII of DENV-3 in Kerala during 2008-2011 epidemics (Manakkadan et al, 2013). It was suggested that high evolutionary rates of certain DENV genotypes and their increased transmission rate between several human hosts in hyperendemic settings may contribute to the emergence of new lineages (Waman et al, 2016).…”

Evolutionary Analysis of Dengue Serotype 2 Viruses Using Phylogenetic and Bayesian Methods from New Delhi, India

“…Lineage replacement in dengue viruses has been reported in many studies [ 25 – 33 ] including India. A lineage replacement event where lineage III replaced lineage I was detected in 2012–2014 in Delhi.…”

Co-Circulation of Dengue Virus Type 3 Genotypes in Vientiane Capital, Lao PDR

“…This particular geographic situation may impact dengue epidemiology in that it may favor the cross boarder movement of viral isolates. A better understanding of DENV movement is now considered as a key point as emergence of new strains or genotypes have been associated with increased clinical severity [12] , [13] , [14] . Our study demonstrated that during the 2012–2013 epidemic, both DENV-3 genotypes II and III detected in Vientiane city were associated with death.…”