Dengue virus envelope protein cross-reactive epitopes (DENV E-protein epitopes)

The Dengue virus envelope (E) protein is the primary surface protein of the virus, mediating host cell attachment and membrane fusion (Kuhn et al., 2002). Cross-reactive epitopes are specific antigenic regions on the E protein that are conserved across the four distinct DENV serotypes and sometimes other flaviviruses (Rouvinski et al., 2015). Key examples include the envelope dimer epitope (EDE), which spans the interface of the E protein dimer, and the highly conserved fusion loop epitope (FLE) (Dejnirattisai et al., 2015). These epitopes are the focus of therapeutic efforts to develop pan-serotype monoclonal antibodies and universal vaccines. However, these sites are also central to antibody-dependent enhancement (ADE), a process where non-neutralizing cross-reactive antibodies facilitate viral entry into Fc-gamma receptor-bearing cells (Halstead, 2003). This mechanism can lead to more severe clinical outcomes, such as Dengue Hemorrhagic Fever or Dengue Shock Syndrome (Screaton et al., 2015). Consequently, drug development targeting these epitopes requires careful engineering to ensure potent neutralization and minimize the risk of ADE (Robinson et al., 2015). Therapeutic antibodies like VIS513 have been designed to target these conserved regions to provide broad protection against all four serotypes (Robinson et al., 2015).

Other names

DENV E protein cross-reactive sitesEnvelope dimer epitopeEDEFusion loop epitopeFLEFlavivirus cross-reactive epitopesDENV complex-reactive epitopes

Neutralization of viral infection by blocking attachment to host cell receptors or inhibiting the conformational change required for membrane fusion.