title: A genomics approach to understanding host response during dengue infection.
abstract: Dengue infection results in a wide clinical spectrum, ranging from asymptomatic, through fever (DF), to the life threatening complications haemorrhagic fever (DHF) and shock syndrome (DSS). Although we now understand that factors such as repeat infections and the type or magnitude of the host response are important in determining severity, the mechanisms of these actions remain largely unknown. Understanding this host-pathogen interaction may enable outcome prediction and new therapy options. Developments in biology now allow a 'systems approach' to be applied to this problem, utilizing whole genomes of both human and virus, in vitro and in vivo to enable a more complete picture of their interplay to be built up. We have developed a chip-based approach to viral sequencing, to increase efficiency and enable large numbers ofgenomes to be completed, together with a web-based interpretation tool. We have also applied human whole genome expression arrays (24000 genes) to characterize the types of host response made to infection and plan to investigate the role of host variation using human whole genome genetic association studies in the future. These technologies have identified novel host pathways involved in viral replication in vitro, and also host immune responses, such as the interferon signalling pathway, that are influenced by viral sequence. This data will be further refined through interlinking with similar data obtained from a large study of dengue patients, initiated in Singapore, that is able to look at the early host response to infection.
authors.affiliation: Genome Institute of Singapore, Biopolis, Singapore 138670.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
authors.forename: Ling
authors.initials: L
authors.lastname: Ling
authors.forename: Thomas
authors.initials: T
authors.lastname: Tolfvenstam
authors.forename: Wayne
authors.initials: W
authors.lastname: Mitchell
authors.forename: Chris
authors.initials: C
authors.lastname: Wong
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Kuznetsov
authors.forename: Joshy
authors.initials: J
authors.lastname: George
authors.forename: Swee-Hoe
authors.initials: SH
authors.lastname: Ong
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
authors.forename: Chia L
authors.initials: CL
authors.lastname: Wei
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.forename: Joshua
authors.initials: J
authors.lastname: Fink
authors.forename: Andy
authors.initials: A
authors.lastname: Yip
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Mark
authors.initials: M
authors.lastname: Schreiber
authors.forename: Subhash G
authors.initials: SG
authors.lastname: Vasudevan
mesh_terms: D000818:Animals; D003715:Dengue / Q000235:genetics* / Q000473:pathology; D003716:Dengue Virus / Q000235:genetics / Q000472:pathogenicity*; D015967:Gene Expression Regulation, Viral; D023281:Genomics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction