Dengue virus nonstructural protein 4B (NS4B) (NS4B)

Dengue virus nonstructural protein 4B (NS4B) is a small, highly hydrophobic integral membrane protein essential for the viral life cycle (UniProt P29978). It localizes to the host endoplasmic reticulum (ER), where it induces membrane curvature to form replication organelles and interacts with other nonstructural proteins, such as NS3, to facilitate viral RNA synthesis (PubMed: 25653451). Beyond its structural role in replication, NS4B is a potent antagonist of the host innate immune response, specifically blocking the interferon (IFN)-alpha/beta signaling pathway by inhibiting STAT1 phosphorylation (PubMed: 15956587). Because of its critical roles in both viral genome replication and immune evasion, NS4B has emerged as a primary target for the development of direct-acting antivirals. Several small-molecule inhibitors, such as JNJ-1802, are currently in development, aiming to disrupt NS4B's function or its interactions with other viral components to treat Dengue virus infections across all four serotypes (PubMed: 34614318).

Other names

NS4B proteinDENV NS4BNon-structural protein 4BDengue virus NS4B

Inhibition of viral replication by disrupting the formation of the viral replication complex, specifically by blocking the interaction between NS4B and NS3, and inhibiting NS4B-mediated antagonism of the host innate immune response (interferon signaling).