Dengue virus induced changes in Ca 2+ homeostasis in human hepatic cells that favor the viral replicative cycle.

The role of Ca ²⁺ during dengue virus (DENV) replication is unknown; thus, changes in Ca ²⁺ homeostasis in DENV infected human hepatic HepG2 and Huh-7 cells were analyzed. Infected HepG2 cells, but not Huh-7 cells, showed a significant increase in plasma membrane permeability to Ca ²⁺ , while both cell lines showed marked reduced levels of Ca ²⁺ stored in the endoplasmic reticulum. While the expression levels of STIM1 and ORAI1 showed no changes, STIM1 and ORAI1 were shown to co-localized in infected cells, indicating activation of the store-operated Ca ²⁺ entry (SOCE) pathway. Finally, manipulation in the infected cells of the intra and extracellular Ca ²⁺ levels by chelators (BAPTA-AM and EGTA), SOC inhibitor (SKF96365), IP3 Receptor antagonist (2APB) or increase of extracellular [Ca ²⁺ ], significantly reduced DENV yield, but not vesicular stomatitis virus yield, used as a control. These results show that DENV infection alters cell Ca ²⁺ homeostasis and that such changes favor viral replication.
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