Genomic Epidemiology of a Dengue Virus Epidemic in Urban Singapore

Novartis Institute for Tropical Diseases, Chromos, Singapore.
Journal of Virology (Impact Factor: 4.44). 03/2009; 83(9):4163-73. DOI: 10.1128/JVI.02445-08
Source: PubMed


Dengue is one of the most important emerging diseases of humans, with no preventative vaccines or antiviral cures available at present. Although one-third of the world's population live at risk of infection, little is known about the pattern and dynamics of dengue virus (DENV) within outbreak situations. By exploiting genomic data from an intensively studied major outbreak, we are able to describe the molecular epidemiology of DENV at a uniquely fine-scaled temporal and spatial resolution. Two DENV serotypes (DENV-1 and DENV-3), and multiple component genotypes, spread concurrently and with similar epidemiological and evolutionary profiles during the initial outbreak phase of a major dengue epidemic that took place in Singapore during 2005. Although DENV-1 and DENV-3 differed in viremia and clinical outcome, there was no evidence for adaptive evolution before, during, or after the outbreak, indicating that ecological or immunological rather than virological factors were the key determinants of epidemic dynamics.

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    • "008 ) and Surabaya ( Yamanaka et al . , 2011 ) . The clustering of all Genotype I samples together with viruses from China , Thailand , and Singapore may suggest that the Genotype I isolates were originated from China , migrated to Thailand and passed Singapore before entering Makassar ( Fig . 1 ) . Genotype IV was predominant in Jakarta in 2004 ( Schreiber et al . , 2009 ) and was also present in Makassar in smaller numbers ."
    Infection Genetics and Evolution 03/2015; · 3.02 Impact Factor
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    • "All viruses used were produced in C6/36 mosquito cells (ATCC). The following patient isolate strains were used: DENV1-05K2916 [EU081234 (29)], DENV2-TSV01 (30), DENV3-VN32/96 (EU482459), and DENV4-2641Y08 (isolated by Environmental Health Institute, Singapore). DENV3-VN32/96 was a gift from Dr. Cameron Simmons, Oxford University Clinical Research Unit, Viet Nam. "
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    ABSTRACT: Dengue virus has four serotypes and is endemic globally in tropical countries. Neither a specific treatment nor an approved vaccine is available, and correlates of protection are not established. The standard neutralization assay cannot differentiate between serotype-specific and serotype cross-reactive antibodies in patients early after infection, leading to an overestimation of the long-term serotype-specific protection of an antibody response. It is known that the cross-reactive response in patients is temporary but few studies have assessed kinetics and potential changes in serum antibody specificity over time. To better define the specificity of polyclonal antibodies during disease and after recovery, longitudinal samples from patients with primary or secondary DENV-2 infection were collected over a period of 1 year. We found that serotype cross-reactive antibodies peaked 3 weeks after infection and subsided within 1 year. Since secondary patients rapidly produced antibodies specific for the virus envelope (E) protein, an E-specific ELISA was superior compared to a virus particle-specific ELISA to identify patients with secondary infections. Dengue infection triggered a massive activation and mobilization of both naïve and memory B cells possibly from lymphoid organs into the blood, providing an explanation for the surge of circulating plasmablasts and the increase in cross-reactive E protein-specific antibodies.
    Frontiers in Immunology 08/2014; 5:388. DOI:10.3389/fimmu.2014.00388
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    • "Viruses in clade Ia and Ib shared clear ancestral lineages with Thai isolates whereas those forming clade Ic could have evolved from another Malaysian isolate seen in 1996 (D1.Malaysia.04834/96). The clade Ic viruses caused the largest major DENV-1 outbreak in Malaysia in 2004 and the viruses shared high sequence similarity to isolates recovered from a major outbreak in Singapore in 2005 [35]. The clade Ic viruses were recovered much earlier in Thailand (1997), China (1998), Cambodia (2001), Vietnam (2002) and Myanmar (2002) before it caused outbreak in Malaysia and Singapore. "
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    ABSTRACT: Recurring dengue outbreaks occur in cyclical pattern in most endemic countries. The recurrences of dengue virus (DENV) infection predispose the population to increased risk of contracting the severe forms of dengue. Understanding the DENV evolutionary mechanism underlying the recurring dengue outbreaks has important implications for epidemic prediction and disease control. We used a set of viral envelope (E) gene to reconstruct the phylogeny of DENV-1 isolated between the periods of 1987--2011 in Malaysia. Phylogenetic analysis of DENV-1 E gene revealed that genotype I virus clade replacements were associated with the cyclical pattern of major DENV-1 outbreaks in Malaysia. A total of 9 non-conservative amino acid substitutions in the DENV-1 E gene consensus were identified; 4 in domain I, 3 in domain II and 2 in domain III. Selection pressure analyses did not reveal any positively selected codon site within the full length E gene sequences (1485 nt, 495 codons). A total of 183 (mean dN/dS = 0.0413) negatively selected sites were found within the Malaysian isolates; neither positive nor negative selection was noted for the remaining 312 codons. All the viruses were cross-neutralized by the respective patient sera suggesting no strong support for immunological advantage of any of the amino acid substitutions. DENV-1 clade replacement is associated with recurrences of major DENV-1 outbreaks in Malaysia. Our findings are consistent with those of other studies that the DENV-1 clade replacement is a stochastic event independent of positive selection.
    BMC Evolutionary Biology 09/2013; 13(1):213. DOI:10.1186/1471-2148-13-213 · 3.37 Impact Factor
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