Vaccinia virus D8 envelope protein (D8) (D8)

The vaccinia virus D8 envelope protein is a 32 kDa type 1 transmembrane protein located on the surface of the intracellular mature virion (IMV) [UniProt, P04195]. It plays a critical role in viral pathogenesis by mediating the adsorption of the virus to host cells through binding with cell surface chondroitin sulfate, particularly the CS-E isoform [Hsiao et al., 1999]. Structurally, D8 features a carbonic anhydrase-like fold with a positively charged crevice that serves as the glycosaminoglycan binding site, although it lacks the enzymatic activity typically associated with carbonic anhydrases [Matho et al., 2012]. As an immunodominant antigen, D8 is a primary target for neutralizing antibodies elicited by smallpox vaccines such as ACAM2000 and JYNNEOS [Matho et al., 2014]. While anti-D8 antibodies can block viral attachment, their neutralizing efficacy is often enhanced by or dependent on the presence of complement [Matho et al., 2012]. Because vaccinia virus utilizes multiple redundant attachment proteins like A27 and H3, therapeutic strategies often involve targeting multiple envelope proteins simultaneously to ensure robust protection against orthopoxvirus infections [NIH]. The protein is also a target for experimental monoclonal antibodies like LA5 and VACV-138, which aim to prevent viral entry by blocking the chondroitin sulfate binding site [Matho et al., 2014].

Other names

D8LProtein D8Cell surface-binding protein OPG10532 kDa protein D8Carbonic anhydrase-like proteinProtein OPG105

Inhibition of viral attachment to host cell chondroitin sulfate