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10 January 2012


A recent article, entitled “Maturation of dengue virus nonstructural protein 4B in monocytes enhances production of dengue hemorrhagic fever-associated chemokines and cytokines”, which appeared in the September 15, 2011 issue of Virology (418:27-39), has been among the most downloaded articles from SciVerse ScienceDirect in the past 90 days. Authored by James F. Kelley, Pakieli H. Kaufusi, Esther M. Volper and Vivek R. Nerurkar, the paper reports that peak secretion of immunomediators (such as IL-6, IL-8, IP-10, TNF-alpha or IFN-gamma) in dengue virus-infected monocytes correlates with maximum virus production and that NS4B and NS5 are primarily responsible for their induction. Furthermore, sequential NS4AB processing initiated by the viral protease NS2B3(pro) significantly enhances immunomediator induction. While the the 2K-signal peptide is not essential for immunomediator induction, it plays a synergistic role with NS4B. These data suggest that NS4B maturation is important during innate immune signaling in dengue virus-infected monocytes. Moreover, these findings suggest that NS4B may be an attractive target for developing flavivirus-wide therapeutic interventions, given the similarities between NS4B topologies and polyprotein processing across flaviviruses.