This would make of NS2B a possible viroporin, causing changes in membrane permeability during DENV infection. Multiple studies have demonstrated the ability of the NS2B protein to oligomerize, producing pore-like structures, and modifying the permeability membranes. While the N and C termini of NS2B are located in the cytoplasm, the central region contains alpha-helical transmembrane domains responsible for the NS2B membrane association. Non-structural protein 2B is a 15-kDa hydrophobic protein that acts as a cofactor of the NS3 protease. NS2A functions in virion assembly: an R84A substitution in NS2A eliminates DENV-2 assembly.NS2A is found to colocalize with viral double-stranded RNA in infected cells and interacts with the 3′ UTR of genomic RNA. The minus-strand RNA then serves as a template to make multiple copies of plus-sense RNA that are packaged to form progeny virions. Upon viral translation, a minus-sense RNA is synthesized from the genomic RNA template, forming a double-stranded RNA. NS2A functions in viral RNA synthesis.NS2A antagonizes the host immune response by inhibiting the interferon response.After flavivirus polyprotein translation, the N terminus of NS2A is cleaved from NS1 by an unknown host protease, and the C terminus is cleaved from NS2B in the cytoplasm by the viral NS2B-NS3 protease-cofactor complex (more details below).Īlthough little is known about the underlying mechanisms, NS2A has been shown to perform three critical functions: Non-structural protein 2A is a 22-kDa hydrophobic transmembrane protein known to associate with the membrane of the endoplasmic reticulum. The NS2 region encodes two proteins, NS2A and NS2B.
NS2, viral RNA synthesis, and virion assembly This month, we continue with this theme and describe other two non-structural proteins of dengue virus, NS2 and NS3. In last month’s blog, we have seen how the glycoprotein NS1 plays an essential role in flavivirus RNA replication.