Isolation of ancestral sylvatic dengue virus type 1, Malaysia.
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ABSTRACT:
SUBMITTER: Teoh BT
PROVIDER: S-EPMC3294529 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Dengue fever is endemic in Malaysia, contributing to significant economic and health burden in the country. Aedes aegypti and Ae. albopictus are the main vectors of the dengue virus (DENV), which circulates in sylvatic and human transmission cycles and has been present in Malaysia for decades. The study investigated the presence and distribution of DENV in urban localities in the Klang Valley, Peninsular Malaysia. A total of 364 Ae. aegypti and 1,025 Ae. albopictus larvae, and 10 Ae. aegypti and 42 Ae. albopictus adult mosquitoes were screened for the presence of DENV. In total, 31 (2.2%) samples were positive, of which 2 Ae. albopictus larvae were co-infected with two serotypes, one with DENV-2 and DENV-3 and the other with DENV-3 and DENV-4. Phylogenetic analysis determined that the isolates belonged to DENV-1 genotype I (1 Ae. aegypti adult), DENV-2 (1 Ae. albopictus larva), DENV-3 genotype V (3 Ae. aegypti larvae and 10 Ae. albopictus larvae) and DENV-4 genotype IV (6 Ae. aegypti larvae and 12 Ae. albopictus larvae), a sylvatic strain of DENV-4 which was most closely related with sylvatic strains isolated from arboreal mosquitoes and sentinel monkeys in Peninsular Malaysia in the 1970s. All four DENV serotypes were co-circulating throughout the study period. The detection of a sylvatic strain of DENV-4 in Ae. aegypti and Ae. albopictus mosquitoes in urban areas in Peninsular Malaysia highlights the susceptibility of these vectors to infection with sylvatic DENV. The infectivity and vector competence of these urban mosquitoes to this strain of the virus needs further investigation, as well as the possibility of the emergence of sylvatic virus into the human transmission cycle.
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Project description:Using phylogenetic analysis of complete virus genomes from human isolates obtained in Nigeria in 1966, we identified sylvatic dengue virus (DENV) strains from 3 febrile patients. This finding extends current understanding of the role of sylvatic DENV in febrile disease and documents another focus of sylvatic DENV transmission in West Africa.
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Project description:Dengue viruses (DENV) are the most important arboviral pathogens in tropical and subtropical regions throughout the world. DENV transmission includes both a sylvatic, enzootic cycle between nonhuman primates and arboreal mosquitoes of the genus Aedes, and an urban, endemic/epidemic cycle between Aedes aegypti, a mosquito with larval development in peridomestic water containers, and human reservoir hosts. All 4 serotypes of endemic DENV evolved independently from ancestral sylvatic viruses and have become both ecologically and evolutionarily distinct; this process may have involved adaptation to (i) peridomestic mosquito vectors and/or (ii) human reservoir hosts. To test the latter hypothesis, we assessed the ability of sylvatic and endemic DENV-2 strains, representing major genotypes from Southeast Asia, West Africa and the Americas, to replicate in two surrogate human model hosts: monocyte-derived, human dendritic cells (moDCs), and mice engrafted with human hepatoma cells. Although the various DENV-2 strains showed significant inter-strain variation in mean replication titers in both models, no overall difference between sylvatic and endemic strains was detected in either model. Our findings suggest that emergence of endemic DENV strains from ancestral sylvatic strains may not have required adaptation to replicate more efficiently in human reservoir hosts, implying that the potential for re-emergence of sylvatic dengue strains into the endemic cycle is high. The shared replication profiles of the American endemic and sylvatic strains suggest that American strains have maintained or regained the ancestral phenotype.
| S-EPMC3608925 | biostudies-literature
Project description:Four serotypes of dengue virus (DENV 1-4) currently circulate between humans and domestic/peridomestic Aedes mosquitoes, resulting in 100 million infections per year. All four serotypes emerged, independently, from sylvatic progenitors transmitted among non-human primates by arboreal Aedes mosquitoes. This study investigated the genetic and phenotypic changes associated with emergence of human DENV-4 from its sylvatic ancestors. Analysis of complete genomes of 3 sylvatic and 4 human strains revealed high conservation of both the 5'- and 3'-untranslated regions but considerable divergence within the open reading frame. Additionally, the two ecotypes did not differ significantly in replication dynamics in cultured human liver (Huh-7), monkey kidney (Vero) or mosquito (C6/36) cells, although significant inter-strain variation within ecotypes was detected. These findings are in partial agreement with previous studies of DENV-2, where human strains produced a larger number of progeny than sylvatic strains in human liver cells but not in monkey or mosquito cells.
| S-EPMC3253985 | biostudies-literature
Project description:The four serotypes of endemic dengue viruses (DENV) circulate between humans and peridomestic Aedes mosquitoes. At present endemic DENV infect 100 million people per year, and a third of the global population is at risk. In contrast, sylvatic DENV strains are maintained in a transmission cycle between nonhuman primates and sylvatic Aedes species, and are evolutionarily and ecologically distinct from endemic DENV strains. Phylogenetic analyses place sylvatic strains basal to each of the endemic serotypes, supporting the hypothesis that each of the endemic DENV serotypes emerged independently from sylvatic ancestors. We utilized complete genome analyses of both sylvatic and endemic DENV serotype 2 (DENV-2) to expand our understanding of their genetic relationships. A high degree of conservation was observed in both the 5'- and 3'-untranslated genome regions, whereas considerable differences at the nucleotide and amino acid levels were observed within the open reading frame. Additionally, replication of the two genotypes was compared in cultured cells, where endemic DENV strains produced a significantly higher output of progeny in human liver cells, but not in monkey kidney or mosquito cells. Understanding the genetic relationships and phenotypic differences between endemic and sylvatic DENV genotypes may provide valuable insight into DENV emergence and guide monitoring of future outbreaks.
| S-EPMC3612928 | biostudies-literature
Project description:Dengue virus (DENV) emerged from the sylvatic environment and colonized urban settings, being sustained in a human-Aedes-human transmission chain, mainly by the bites of females of the anthropophilic species Aedes aegypti. Herein, we sought evidence for fine-tuning in viral codon usage, possibly due to viral adaptation to human transmission. We compared the codon adaptation of DENV serotype 2 (DENV-2) genotypes from urban and sylvatic habitats and tried to correlate the findings with key evolutionary determinants. We found that DENV-2 codons of urban and sylvatic genotypes had a higher CAI to humans than to Ae. aegypti. Remarkably, we found no significant differences in codon adaptation to human between urban American/Asian and sylvatic DENV-2 genotypes. Moreover, CAI values were significantly different, when comparing all genotypes to Ae. aegypti codon preferences, with lower values for sylvatic than urban genotypes. In summary, our findings suggest the presence of a molecular signature among the genotypes that circulate in sylvatic and urban environments, and may help explain the trafficking of DENV-2 strains to an urban cycle.
| S-EPMC7106335 | biostudies-literature
Project description:Sylvatic dengue viruses (DENV) are transmitted in an enzootic cycle between nonhuman primates and arboreal Aedes mosquitoes in Southeast Asia and West Africa. Although previous analyses have revealed the evolutionary processes among endemic (human) DENV, little is known about viral evolution in the sylvatic cycle. Through an analysis of 14 complete coding regions of sylvatic Dengue type 2 virus sampled over a 33-year period, we show that both the rate of evolutionary change and the pattern of natural selection are similar among endemic and sylvatic DENV, although the latter have a uniquely high frequency of positive selection in the NS4B protein gene. Our findings support a recent cross-species transmission event and suggest the possibility of future DENV reemergence from the sylvatic cycle.
| S-EPMC1951459 | biostudies-literature
Project description: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.
| S-EPMC5921268 | biostudies-literature
Project description:Dengue viruses circulate in both human and sylvatic cycles. Although dengue viruses (DENV) infecting humans can cause major epidemics and severe disease, relatively little is known about the epidemiology and etiology of sylvatic dengue viruses. A 20-year-old male developed dengue hemorrhagic fever (DHF) with thrombocytopenia (12,000/ul) and a raised hematocrit (29.5% above baseline) in January 2008 in Malaysia. Dengue virus serotype 2 was isolated from his blood on day 4 of fever. A phylogenetic analysis of the complete genome sequence revealed that this virus was a member of a sylvatic lineage of DENV-2 and most closely related to a virus isolated from a sentinel monkey in Malaysia in 1970. This is the first identification of a sylvatic DENV circulating in Asia since 1975.
| S-EPMC2669127 | biostudies-literature
Project description:OBJECTIVE:Detection of different serotypes of dengue virus and provide information on origin, distribution and genotype of the virus. METHODS:Dengue virus serotypes identified as DEN-1 and DEN-2 were amplified and sequenced with E gene. The consensus sequences were aligned with references E gene sequences of globally available GenBank. Phylogenetic analysis was performed using Neighbor-joining and Kimura 2-parameter model to construct phylogenetic tree. RESULTS:A total of 53 dengue virus isolates were positive, of which 38 (71.7%) were DENV-1 and 15 (28.3%) were DENV-2. Phylogenetic tree of DENV-1 and DENV-2 showed that the isolates were clustered in genotype I and cosmopolitan genotype, respectively considered the predominant genotypes in Southeast Asian countries. The molecular epidemiology genotype I DENV-1 and cosmopolitan genotype DENV-2 have been co-circulating in Klang Valley areas, Malaysia without shifting of genotype. CONCLUSION:The study reveals that DENV-1 and DENV-2 have been circulating in Malaysia. The isolates are clustered in genotype 1 and cosmopolitian genotype, respectively. The study results would help in planning for prevention and control of dengue virus in Malaysia.
| S-EPMC4485282 | biostudies-literature