Dengue virus serotype 4 pre-membrane and envelope proteins (DENV-4 prM/E)

The Dengue virus serotype 4 (DENV-4) pre-membrane (prM) and envelope (E) proteins are the primary structural components of the DENV-4 virion surface. The E protein is a class II fusion protein responsible for binding to host cell receptors and mediating the pH-dependent fusion of the viral and endosomal membranes (UniProt: P09866). The prM protein serves as a chaperone during viral assembly, protecting the E protein from premature fusion as it moves through the acidic environment of the trans-Golgi network (PubMed: PMC4070680). Together, these antigens are the principal targets for neutralizing antibodies and are the core components of recombinant and live-attenuated vaccines, such as Dengvaxia and Qdenga (WHO: Dengue vaccines). In clinical settings, targeting these proteins is essential for preventing Dengue fever and its severe manifestations, including Dengue Hemorrhagic Fever and Dengue Shock Syndrome. However, a significant challenge in targeting these antigens is the risk of antibody-dependent enhancement (ADE), where non-neutralizing or sub-neutralizing antibodies against prM/E can facilitate viral entry into Fc-receptor-bearing cells, potentially worsening the disease (Nature Reviews Microbiology: 10.1038/nrmicro.2016.158).

Other names

DENV-4 E proteinDENV-4 prM proteinDengue virus type 4 envelope glycoproteinDENV-4 structural proteinsDENV-4 prM/E antigens

Vaccines and therapeutic antibodies targeting these antigens work by inducing or providing neutralizing antibodies that bind to the E protein. This binding blocks the virus's ability to attach to host cell receptors and prevents the structural rearrangements necessary for membrane fusion within the endosome, thereby neutralizing viral infectivity (PubMed: 28407471, 25540958).