Cell surface-binding protein D8 (D8)

The Cell surface-binding protein D8 is a 32-kDa type 1 transmembrane protein located on the envelope of the Vaccinia virus intracellular mature virion (IMV). It possesses a structural fold homologous to carbonic anhydrases, although it lacks catalytic activity; instead, this fold has evolved to bind specifically to chondroitin sulfate on the surface of host cells, facilitating viral adsorption and entry (Matho et al., 2012; Hsiao et al., 1999). D8 is recognized as an immunodominant antigen, making it a primary target for the neutralizing antibody response elicited by smallpox vaccines such as ACAM2000 and JYNNEOS (Matho et al., 2014). While D8 is not strictly essential for viral replication in vitro, its deletion significantly reduces viral infectivity and pathogenesis in vivo, highlighting its importance as a therapeutic target. Current drug development efforts focus on monoclonal antibodies that block the D8-chondroitin sulfate interaction and the inclusion of D8 in next-generation recombinant subunit vaccines to provide broad protection against orthopoxviruses, including variola and monkeypox viruses (Schmaljohn et al., 2012).

Other names

D8LVaccinia virus D8 proteinCarbonic anhydrase homologChondroitin sulfate-binding protein32 kDa envelope protein

Inhibition of viral attachment to host cell chondroitin sulfate and complement-dependent neutralization of the virion.