DENV has also been shown to express inhibitors of the type I IFN signaling cascade [26] and has been shown to encode for at least four non-structural proteins NS2A, NS4A, NS4B and NS5 that target different components of this pathway. The most remarkable example is the proteasomal degradation of human STAT2 by the NS5, a phenomenon that does not occur in mouse cells, which makes mouse STAT2 a restriction factor for DENV replication in these animals [27, 28, 29, 30, 31] . In summary, DENV can successfully inhibit two fundamental steps of the innate immune system, both the inhibition of the type I IFN production and the signaling. In this way, DENV reduces the expression of hundreds of interferon inducible genes that would otherwise establish the antiviral state and control the spread of the infection in the host.