Comparative Analysis of Full-Length Genomic Sequences of 10 Dengue Serotype 1 Viruses Associated with Different Genotypes, Epidemics, and Disease Severity Isolated in Thailand over 22 Years

Abstract

Abstract. Comparative sequence analysis was performed on the full-length genomic sequences of 10 representative dengue virus serotype 1 (DENV-1) strains sampled from patients at Children's Hospital, Bangkok, Thailand over a 22-year period, which represented different epidemics, disease severity, and sampling time. The results showed remarkable inter-genotypic variation between predominant and non-predominant genotypes and genotype-specific amino acids and nucleotides throughout the entire viral genome except for the 5′-non-translated region. The frequency of intra-genotypic variation was correlated with dengue transmission rate and sampling time. The 5′-non-translated region of all 10 viruses was highly conserved for predominant and non-predominant genotypes and NS2B was the most conserved protein. Some intra-genotypic substitutions of amino acids and nucleotides in predominant genotype strains were fixed in the viral genome since 1994, which indicated that the evolution of predominant genotype strains in situ over time might contribute to increased virus fitness important for sustaining dengue epidemics in Thailand.

Nucleotide substitutions in dengue virus serotypes from Asian and American countries: insights into intracodon recombination and purifying selection

“…These studies suggested adaptive evolution of DENV in natural populations but indicated that the adaptive selection pressures differ among serotypes, genotypes and the encoded proteins of the virus. Furthermore, fixation of beneficial mutations may lead to virus evolution with altered antigenicity, virulence, or tissue tropism; and eventually influence disease patterns and transmission [17]. Similarly, genetic recombination is also a significant factor in diversity of DENV in natural populations [18].…”

Challenges in dengue research: A computational perspective

“…Dengue virus is a surprisingly conserved RNA virus (Choudhury, Lott, Banu, Cheng, & Teo, ; Lequime, Fontaine, Ar Gouilh, Moltini‐Conclois, & Lambrechts, ; Thai, Henn, Zody, Tricou, & Nguyet, ; Amarilla, de Almeida, Jorge, Alfonso, & de Castro‐Jorge, ; Holmes, ). Even though its serotypes present seemingly competitive dynamics, similar to the behaviour of antigenic strains of other fast evolving pathogens, observations of positive selection are rare (Tang et al., ; Filomatori et al., ; Waman et al., ; Hang et al., ; Choudhury et al., ; Martin, Chirivella, Co, Santiago, & Gubler, ; Sim, Aw, Wilm, Teoh, & Hue, ). Dengue transmission models have offered insight, but have so far failed to reach consensus on the possible biological drivers of the observed dynamic behaviour.…”

“…There are also reports of sporadic episodes of positive selection and fixation of particular lineages (Tang et al., ; Filomatori et al., ; Waman et al., ; Hang et al., ; Choudhury et al., ; Martin et al., ), and it is generally believed that most events of lineage replacement go unnoticed, as the majority of endemic regions rely on syndromic surveillance, and as these events are not expected to result in significant changes in disease incidence (Lourenço & Recker, ). While there are rare examples of well‐described lineage shifts in the literature (OhAinle et al., ; Bennett, Holmes, Chirivella, Rodriguez, & Beltran, ), not much is known about the epidemiological and ecological contexts in which emergence of fitter lineages is favoured.…”

“…Since then, a wide number of sylvatic strains (i.e., of animal origin) have been isolated and reported to belong to each of the lineages of human‐bearing serotypes, proposing a zoonotic origin for the pathogen (Holmes & Twiddy, ). Introduction of each serotype into the human population was extrapolated to have taken place at different time points, with DENV2's most recent common ancestor being the oldest, estimated to be approximately 1,000 years old (Twiddy, Holmes, & Rambaut, ; Weaver & Vasilakis, ), roughly corresponding to some of the first reports of dengue‐like illnesses (Vasilakis & Weaver, ; Tang et al., ; Weaver & Vasilakis, ). The genetic distance between currently circulating serotypes is likely a by‐product of allopatric evolution due to ecological partitioning of ancestral sylvatic strains (Holmes & Twiddy, ; Weaver & Vasilakis, ).…”

“…Within each serotype, nucleic acid sequencing techniques have identified genetic subgroups or lineages, commonly denominated as dengue genotypes (Tang et al., ; Weaver & Vasilakis, ). Notably, the overall amino acid sequence similarity among genotypes is generally above 90% (Holmes & Twiddy, ; Leitmeyer et al., ), whereas between serotypes, it can range between 60% and 80% (Irie, Mohan, Sasaguri, Putnak, & Padmanabhan, ; Rothman, ).…”