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Abstract Background While dengue-elicited early and transient host responses preceding defervescence could shape the disease outcome and reveal mechanisms of the disease pathogenesis, assessment of these responses are difficult as patients rarely seek healthcare during the first days of benign fever and thus data are lacking. Methods In this study, focusing on early recruitment, we performed whole-blood transcriptional profiling on denguevirus PCR positive patients sampled within 72 h of self-reported fever presentation (average 43 h, SD 18.6 h) and compared the signatures with autologous samples drawn at defervescence and convalescence and to control patients with fever of other etiology. Results In the early dengue fever phase, a strong activation of the innate immune response related genes were seen that was absent at defervescence (4-7 days after fever debut), while at this second sampling genes related to biosynthesis and metabolism dominated. Transcripts relating to the adaptive immune response were over-expressed in the second sampling point with sustained activation at the third sampling. On an individual gene level, significant enrichment of transcripts early in dengue disease were chemokines CCL2 (MCP-1), CCL8 (MCP-2), CXCL10 (IP-10) and CCL3 (MIP-1α), antimicrobial peptide β-defensin 1 (DEFB1), desmosome/intermediate junction component plakoglobin (JUP) and a microRNA which may negatively regulate pro-inflammatory cytokines in dengue infected peripheral blood cells, mIR-147 (NMES1). Conclusions These data show that the early response in patients mimics those previously described in vitro, where early assessment of transcriptional responses has been easily obtained. Several of the early transcripts identified may be affected by or mediate the pathogenesis and deserve further assessment at this timepoint in correlation to severe disease.

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. [ABSTRACT FROM AUTHOR]

Abstract: DengueInfo (http://www.dengueinfo.org) is a web portal and database that brings clarity to dengue research by integrating the growing number of complete genome sequences of dengue virus with relevant literature and curated epidemiological information. Additionally, it represents a repository of on-going prospective and retrospective studies of dengue disease severity. We intend the database to be a flagship resource for the dengue community, providing standardized and high quality information and facilitating research into key aspects of dengue biology and assisting in its control. To aid this process we also introduce a standard nomenclature for dengue isolates inspired by globally accepted system used for influenza virus. [Copyright &y& Elsevier]

Abstract: The availability of whole genome sequencing has contributed to many aspects of dengue research, and its use in dengue virus (DENV) surveillance for early epidemic warning has been proposed. Methods to sequence the genomes of individual dengue serotypes have been described previously, but no single method is known to be applicable for all four serotypes. This report describes a method for sequencing the entire genome of all four DENV serotypes. Using tagged oligonucleotide primers designed for the 3′ end, viral RNA was reverse transcribed into a cDNA spanning the entire genome of each of the four serotypes (DENV-1 to -4). This was followed by amplification of the entire cDNA in five overlapping amplicons. A sequence tag was added to the sense primer annealing to the 5′ UTR sequence and the antisense primer annealing to the 3′ UTR sequence to ensure no terminal nucleotides were omitted during PCR. Sixty-one virus isolates were sequenced: 58 DENV-2, one DENV-1, one DENV-4 and one DENV-3 published previously. The method described could be applied readily for viral biology studies and incorporated into proactive dengue virologic surveillance. [ABSTRACT FROM AUTHOR]