Dengue virus type 2 pre-membrane protein (prM)

The Dengue virus type 2 pre-membrane protein (prM) is a critical structural component of the Dengue virus (DENV-2) virion, essential for the assembly and maturation of infectious particles (UniProt P07563). It functions primarily as a chaperone for the envelope (E) protein during viral assembly in the endoplasmic reticulum, forming prM-E heterodimers that prevent the E protein from undergoing premature, low-pH-triggered conformational changes during transit through the secretory pathway (Pierson & Diamond, 2012). Just prior to viral release, the host cell protease furin cleaves prM into the pr peptide and the mature M protein, a step required for the virus to become fully infectious (Rodenhuis-Zybert et al., 2010). In the context of therapeutics, prM is a primary antigen in several live-attenuated and recombinant vaccines, such as Dengvaxia and Qdenga, which aim to elicit a protective immune response (EMA, 2022). However, prM is also a significant factor in the pathogenesis of severe Dengue; non-neutralizing antibodies against prM can facilitate antibody-dependent enhancement (ADE), where the virus more easily infects Fc-receptor-bearing cells, potentially leading to Dengue Hemorrhagic Fever or Dengue Shock Syndrome (Dejnirattisai et al., 2010). Consequently, prM remains a complex target that requires careful consideration in vaccine design to ensure the induction of neutralizing rather than sensitizing antibodies.

Other names

prM proteinPre-membrane proteinMembrane glycoprotein precursorDENV-2 prMDengue virus 2 prM

Vaccines containing the prM protein induce the production of neutralizing antibodies that bind to the virion surface, preventing viral attachment and entry into host cells (FDA, 2019). Additionally, targeting the prM-E complex can inhibit the maturation process by preventing the host protease furin from cleaving prM into the mature M protein, thereby rendering the virus non-infectious (Rodenhuis-Zybert et al., 2010).