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Review
. 2006 Dec;80(23):11418-31.
doi: 10.1128/JVI.01257-06. Epub 2006 Aug 23.

Recent advances in deciphering viral and host determinants of dengue virus replication and pathogenesis

Karen Clyde  1 , Jennifer L Kyle, Eva Harris
Affiliations
Review

Recent advances in deciphering viral and host determinants of dengue virus replication and pathogenesis

Karen Clyde et al. J Virol. 2006 Dec.
No abstract available

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
Intracellular life cycle of dengue virus. DENV binds (step 1) and enters (step 2) cells via an uncharacterized receptor(s) by RME. Endosomal acidification (step 3) results in an irreversible trimerization of the viral E protein, exposing the fusion domain. After being uncoated, the vRNA is translated (step 4) at ER-derived membranes, where it is processed into three structural and seven NS proteins. After the viral replication complex is synthesized, vRNA translation switches off and RNA synthesis (step 5) begins. Subsequently, successive rounds of translation (step 6) are followed by assembly in the ER. The virion is maturated in the Golgi compartment (step 7) and exits via the host secretory pathway. Viral proteins C, E, NS3, and NS5 have been observed in the nuclei of infected cells (57, 96, 177, 186, 190), and the vRNA associates specifically with a number of cellular proteins (41, 58, 187, 198); however, the biological significance is unknown. L-SIGN, liver/lymph node-specific ICAM-3-grabbing nonintegrin; PTB, polypyrimidine tract binding protein; EF-1α, elongation factor 1α; hnRNP L, heterogeneous nuclear ribonucleoprotein L; PDI, protein disulfide isomerase.
FIG. 2.
FIG. 2.
Structure of the dengue virus genome. DENV vRNA contains a 5′ type 1 cap structure, and the single open reading frame is flanked by 5′ and 3′ UTRs. Conserved RNA secondary structures in the UTRs and in the coding region have been determined to function at various stages of the viral life cycle. Functions for several of the viral proteins have been determined; however, many remain to be elucidated. The secondary structure is based on Southeast Asian strains of DENV2 and is similar for different strains and serotypes. Structures designated cHP, CS, UAR, DB1, DB2 and 3′SL were compiled from a combination of computer predictions, functional analyses, and solution structure probing (3, 34, 71, 132, 148, 154). RdRP, RNA-dependent RNA polymerase; DB, dumbbell.
FIG. 3.
FIG. 3.
Pathogenesis of dengue virus infection. DENV initially infects a cell of the dendritic cell/macrophage/monocyte line (reviewed in reference 5) via receptor-mediated endocytosis and/or enhanced uptake via antibody-virus complexes attached to Fcγ receptors (reviewed in references and 73). TNF-α (22, 52) and NO (24, 141) are produced primarily by infected monocytes/macrophages and activate endothelial cells, which can contribute to increased vascular permeability (reviewed in reference 17). Changes in vascular permeability in DENV infections have classically been measured by monitoring levels of albumin in the plasma (195). IFN-γ is produced primarily by NK and CD8+ T cells and activates macrophages as well as CD4+ T cells (17). High levels of DENV and sNS1 circulate in the bloodstream (9, 114), and both have been shown to circulate as immune complexes as well. FcγR, Fc gamma receptor.
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