AurKB activity is necessary for Dengue virus release

Flaviviruses, such as Dengue (DENV), Zika and Yellow Fever are pathogens with high morbidity and mortality. Around 390 million people per year are infected with DENV, and almost 90 million develop the clinical forms of the infection. In the present work, we analyzed the role of Aurora Kinase B (AurKB) in the replicative cycle of DENV. This Kinase regulates the activation of ESCRT-III complex, which has an essential role in the viral morphogenesis and/or budding from RE to Golgi apparatus. The compound ZM 447439 (ZM) was used to inhibit specifically AurKB, and the viral progeny, viral RNA/protein synthesis efficiency and NS1 secretion were evaluated. The kinase inhibition did not alter the viral protein production/secretion or genome replication but impaired the viral yield without altering the percentage of infected cells.

Moreover, confocal microscopy analysis of DENV-infected ZM447439-treated cells shows a delocalization of viral components from the replicative complexes. In summary, these observations indicate that AurKB participates in DENV viral morphogenesis or release. Together, our results suggest possible participation of AurKB in the viral release of budding through activation of the ESCRT-III complex and suggest a new role for AurKB on flavivirus viral cycle.