Emergence of the Asian lineage dengue virus type 3 genotype III in Malaysia

Abstract

BackgroundDengue virus type 3 genotype III (DENV3/III) is associated with increased number of severe infections when it emerged in the Americas and Asia. We had previously demonstrated that the DENV3/III was introduced into Malaysia in the late 2000s. We investigated the genetic diversity of DENV3/III strains recovered from Malaysia and examined their phylogenetic relationships against other DENV3/III strains isolated globally.ResultsPhylogenetic analysis revealed at least four distinct DENV3/III lineages. Two of the lineages (DENV3/III-B and DENV3/III-C) are current actively circulating whereas the DENV3/III-A and DENV3/III-D were no longer recovered since the 1980s. Selection pressure analysis revealed strong evidence of positive selection on a number of amino acid sites in PrM, E, NS1, NS2a, NS2b, NS3, NS4a, and NS5. The Malaysian DENV3/III isolates recovered in the 1980s (MY.59538/1987) clustered into DENV3/III-B, which was the lineage with cosmopolitan distribution consisting of strains actively circulating in the Americas, Africa, and Asia. The Malaysian isolates recovered after the 2000s clustered within DENV3/III-C. This DENV3/III-C lineage displayed a more restricted geographical distribution and consisted of isolates recovered from Asia, denoted as the Asian lineage. Amino acid variation sites in NS5 (NS5–553I/M, NS5–629 T, and NS5–820E) differentiated the DENV3/III-C from other DENV3 viruses. The codon 629 of NS5 was identified as a positively selected site. While the NS5-698R was identified as unique to the genome of DENV3/III-C3. Phylogeographic results suggested that the recent Malaysian DENV3/III-C was likely to have been introduced from Singapore in 2008 and became endemic. From Malaysia, the virus subsequently spread into Taiwan and Thailand in the early part of the 2010s and later reintroduced into Singapore in 2013.ConclusionsDistinct clustering of the Malaysian old and new DENV3/III isolates suggests that the currently circulating DENV3/III in Malaysia did not descend directly from the strains recovered during the 1980s. Phylogenetic analyses and common genetic traits in the genome of the strains and those from the neighboring countries suggest that the Malaysian DENV3/III is likely to have been introduced from the neighboring regions. Malaysia, however, serves as one of the sources of the recent regional spread of DENV3/III-C3 within the Asia region.Electronic supplementary materialThe online version of this article (10.1186/s12862-018-1175-4) contains supplementary material, which is available to authorized users.

Emergence of genotype Cosmopolitan of dengue virus type 2 and genotype III of dengue virus type 3 in Thailand

“…In the present study, the DENV-3 genotype III tMRCA was estimated (based on envelope-encoding sequences) to be 1949 (95% HPD: 1936.1–1963.6), consistent with the previous study [ 73 ]. However, this value (again, obtained based on envelope-encoding sequences) differed from the tMRCA of 1967 (95% HPD: 1965–1969) reported by Tan et al [ 74 ] based on analysis of the complete viral coding sequence. This difference might be due to the fact that the oldest virus in our analysis was from 1966 (JQ868069) and represented an isolate from which only the envelope sequence was available.…”

“…Outside of Thailand, DENV-3 genotype III also has been disseminated to other countries in Asia. DENV-3 genotype III was isolated as a minor genotype in Laos in 2012–2013 [ 76 ], and was first observed in Vietnam in 2013 [ 77 ], in Singapore in 2013 [ 78 ], and in Malaysia in 2008–2010 [ 74 ]. Our study revealed that the DENV-3 genotype III currently circulating in Thailand clusters with lineage-C viruses from South Asia (India and Pakistan) and from other areas in Southeast Asia (Singapore, Laos, and Viet Nam) where the virus had been detected; this cluster was independent of the lineage-A viruses (recovered from Sri Lanka, Malaysia, and Singapore) and the lineage-B viruses obtained in the Americas.…”

Phylogenetic analysis revealed the co-circulation of four dengue virus serotypes in Southern Thailand

“…However, even though it was proposed that the hyperendemicity could aggravate the frequency of dengue severe symptoms, the relationship between concurrent infection and disease severity remain contradictory, with variable conclusions depending on the studies [17]. The co-circulation and the replacement of genotype are also associated with virulence and have already been reported [18–21]. In Thailand, genotype replacement for DENV-2 and DENV-3 was reported during the 1980’s and the 1990’s, respectively [22, 23].…”

Current vector research challenges in the greater Mekong subregion for dengue, Malaria, and Other Vector-Borne Diseases: A report from a multisectoral workshop March 2019

“…However, patterns of inapparent infection rates are heterogenous, further confounding efforts to estimate transmission intensity [151][152][153][154][155]. While cost-effective and easyto-use rapid diagnostics exist for DENV, a lack of specific and consistently performing diagnostics contributes to this problem, especially in regions where genetically related viruses cocirculate, leading to misclassification of positive results [156][157][158][159][160][161][162][163][164][165][166][167][168][169]. Diagnostic tools for tickborne diseases relevant to the region are nonexistent, and this has hampered confirmation of infection, identification of pathogen, and conduct of surveillance.…”