Successful DENV infection relies on its ability to evade the host innate immune system. By using iTRAQ
labeling followed by LC-MS/MS analysis, DDX21 was identified as a new host RNA helicase involved in
the DENV life cycle. In DENV infected cells, DDX21 translocates from nucleus to cytoplasm to active the
innate immune response and thus inhibits DENV replication in the early stages of infection. DDX21 is
then degraded by the viral NS2B-NS3 protease complex and the innate immunity is thus subverted to
facilitate DENV replication. The results reveal a new mechanism in which DENV subverts the host innate
immune system to facilitate its replication in host cells.