Immune system interaction In recent years, many studies have shown that flaviviruses, especially dengue virus, has the ability to inhibit the innate immune response during the infection. Indeed, dengue virus has many nonstructural proteins that allow the inhibition of various mediators of the innate immune system response. These proteins act on two levels : Inhibition of interferon signaling by blocking signal transducerNS4B is a small, hydrophobic protein located in association with the endoplasmic reticulum. It may block the phosphorylation of STAT 1 after induction by interferons type I alpha & beta. In fact, as the activity of Tyk2 kinase decreases in association with dengue virus, so too does STAT 1 phosphorylation. Furthermore, the innate immune system's response to the virus is further damped as expression of interferon-stimulating gene(s) (ISG) is restricted by the aforementioned 'NS4B' protein. NS2A and NS4A cofactor may also take part in the STAT 1 inhibition.NS5 - the presence of this 105-kDa protein results in inactivation of STAT2 (via the signal transduction of the response to interferon) when it is expressed alone. When NS5 is cleaved with NS4B by a protease (NS2B3), it can degrade STAT2. In fact, after the cleavage of NS5 by the protease, an E3 ligase association with STAT2 occurs, and the E3 ligase targets STAT2 for the degradation. Inhibition of the type I interferon response NS2B3-b protease complex is a proteolytic core consisting of the last 40 amino acids of NS2B and the first 180 amino acids of NS3. Cleavage of the NS2B3 precursor activates the protease complex. This protease complex allows the inhibition of the production of type I interferon by reducing the activity of IFN-beta promoter; NS2B3 protease complex is involved in inhibiting the phosphorylation of IRF3. The NS2B3 protease complex inhibits (by cleaving) protein MITA which allows the IRF3 activation. Mosquito D7 saliva protein Dengue virus is transmitted by the mosquito species Aedes aegypti, which produces saliva that contains over 100 unique proteins, including the protein family D7. Scientists used to believe that A. aegypti saliva, when being transmitted, actually enhanced dengue virus in the body. The mosquito's saliva was thought to make the virus spread faster due to the weakened immune response of its host. However, a current study has found that the protein D7 hinders the virus transmission into the host cells. The immune responses of antibodies that are trying to fight off the foreign virus actually increase