Our TLDA results indicated that there was significant upregulation of a number of ubiquitin-proteasome system related genes during dengue virus replication but it was unclear if this response was anti-viral or if the dengue virus utilised components of the ubiquitin-proteasome system for replication. Use of proteasome inhibitors, MG-132 and ALLN, significantly reduced the release of dengue virus following infection of the HepG2 cell line. Previously, it has been shown that the effect of proteasome inhibitors may be virus specific with these compounds less (or non-) effective against virus such as influenza [45] and equine infectious anemia virus [46] . The effect of proteasome inhibition on viral replication appears to be mediated via a number of different processes including the involvement of ubiquitin or the proteasome in virus assembly [45] , budding [47] and release and maturation [48] . Further studies may elucidate the exact role the ubiquitin-proteasome plays in dengue virus replication which may involve trafficking of the virus to the plasma membrane or the maturation and fusion of the virus upon release [49] . It is instructive to compare our results with those of a published microarray study investigating host responses in patient blood [50] . That study identified genes whose protein products are expressed in the ER to be the most significantly enriched, which directly overlaps with our identification of the ubiquitin pathway; specifically including UBE2 and the PSMB genes. This may represent a process fundamental to viral replication in any system. In addition, Simmons et al. described host responses associated with dengue shock syndrome that clearly overlap with our interferon related gene list. In particular, G1P genes, OAS genes, IFI genes and Mx genes were found in both studies, suggesting that the amount of viral replication may be directly related to clinical outcome.