Comparative complete genome analysis of dengue virus type 3 circulating in India between 2003 and 2008

Abstract

Dengue is endemic in most parts of the tropics including India. So far, complete genome information for Indian dengue isolates is not available. In the present study, we characterized the genome of three dengue type 3 viruses isolated from India. The genomes of all three viruses were found to be 10 707 bp long with an ORF encoding 3390 aa. Extensive molecular phylogenetic analysis based on comparison of the complete genome and envelope gene classified the recent Indian viruses into genotype III (lineage III), revealing a shift of lineage from lineage V. The sequence analysis revealed several non-conservative changes in major structural proteins. This study clearly indicates that the genotype III (lineage III) dengue type 3 viruses have been continuously circulating in major parts of India since 2003 and are responsible for the recent major outbreaks all over India. This is the first extensive study on complete genome analysis of dengue type 3 viruses in India.Dengue/dengue haemorrhagic fever (DF/DHF) has emerged as the most important mosquito-borne human viral infection of the 21st century. An estimated 100 million dengue infections are now reported annually around the world. Dengue is caused by four antigenically and genetically distinct, single-stranded positive-sense RNA viruses designated dengue virus types 1-4 (DENV-1-4). Dengue viruses belong to the genus Flavivirus of the family Flaviviridae. The genome of dengue virus is approximately 10.7 kb in length and contains a single ORF that encodes three structural [capsid (C), premembrane (prM) and envelope (E)] and seven non-structural (NS) proteins (NS1, Ns2a, NS2b, NS3, NS4a, NS4b and NS5) (Gubler, 1998).Dengue infection is characterized by a spectrum of illness ranging from mild, self-limiting dengue fever to lifethreatening dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). The pathogenesis of DHF and DSS is poorly understood. However, several hypotheses, such as antibody dependent enhancement in heterotypic secondary dengue infections, involvement of a virulent viral genotype and host factors, have been suggested to explain this mechanism (Leitmeyer et al., 1999;Rico-Hesse et al., 1997;Messer et al., 2003).All the DENV serotypes are further classified into multiple subtypes/genotypes based on their genomic diversity (Weaver & Vasilakis, 2009). Five distinct genotypes of DENV-3 have been identified to date (Lanciotti et al., 1994;Wittke et al., 2002;Uzcategui et al., 2003). Genotypes I-III are responsible for most DENV-3 infections and have been associated with DF/DHF epidemics in South East Asia, the Indian subcontinent, the south Pacific, East Africa and the Americas. Genotypes IV and V were not associated with DHF epidemics and are only represented by a few early sequences from the Americas, the south Pacific and Asia, with the exception of recent reports regarding genotype V-related cases from Brazil and Colombia (Aquino et al., 2009).In India, the frequency of DHF outbreaks have increased at an alarming rate over the past 15 years. Deng...

Distribution and phylogenetic analysis of Culex flavivirus in mosquitoes in China

“…Culex flavivirus in mosquitoes in China genotypes is the criterion used to classify most flaviviruses into genotypes [1,16,24,25]. The differences between the nucleotide sequences of the Chinese group and those of the other two subgroups were approximately 5 %.…”

Co-circulation of two genotypes of dengue virus serotype 3 in Guangzhou, China, 2009

“…Since DENV-1 has circulated in Guangzhou for about ten years, the new DENV-3 has potential to increase the rate of secondary heterotypic infection. Furthermore, the previous studies showed that epidemic DHF has appeared in association with DENV-3 [31-33]. In the Americas, DENV-3 presented greater epidemic potential and virulence [20].…”

“…All these genotype III DENV-3 strains were closely related to those sampled in India in 2007 and 2008, suggesting these Chinese isolates might be imported from India. Previously, the introduction of new genotype III of DENV-3 has been recognized as one of the factors leading to the emergence of DHF in Pakistan and India [33,36]. These strains are therefore interesting and their virological characterization and virulence analyses are currently underway.…”

Re-Emergence of Dengue Virus Type 3 in Canton, China, 2009–2010, Associated with Multiple Introductions through Different Geographical Routes

“…Epidemiologic data strongly suggested that the first autochthonous case was directly linked to the first index case who returned from Vietnam. Phylogenetic analysis showed that the isolate (09/GZ/1483) of the first autochthonous case and the DENV-3 strain (09/GZ/1081) from the first index case shared 99.8% nucleotidic identity and were grouped together in the same clade which belonged to DENV-3 genotype V. Genotype V was seldom associated with dengue epidemics and is only represented by a few early sequences from the Asia, with the exception of recent reports from Brazil and Colombia [24], [25]. Despite an active search of symptomatic cases among their close contacts and in the neighbourhood, no other cases were identified.…”