Envelope protein H3 (H3L) (H3L)

Vaccinia virus H3L (Envelope protein H3) is an immunodominant protein located on the envelope of the intracellular mature virion (IMV), the most abundant infectious form of the virus (Lin et al., 2000; Davies et al., 2005). It plays a critical dual role in the viral life cycle: it facilitates viral attachment to host cells by binding to cell-surface heparan sulfate and is essential for virion morphogenesis, specifically the transition from immature to mature virions (Lin et al., 2000; Singh et al., 2012). Structurally, H3L possesses a glycosyltransferase-like fold and has been shown to bind UDP-glucose, although its specific enzymatic activity remains a subject of investigation (Singh et al., 2012). As a major target of the human neutralizing antibody response following smallpox vaccination, H3L is a key component in the development of subunit vaccines and therapeutic antibodies against orthopoxviruses (Davies et al., 2005). Its high conservation across the Orthopoxvirus genus makes it a valuable target for broad-spectrum poxvirus countermeasures, including those for monkeypox and variola virus (Singh et al., 2012; Shcherbakov et al., 2022). In animal models, immunization with recombinant H3L protein has been shown to elicit high titers of neutralizing antibodies and provide protection against lethal viral challenges (Davies et al., 2005). Furthermore, H3L is being explored as a target for deimmunization in the development of oncolytic vaccinia virus strains to reduce antiviral immune clearance (Shcherbakov et al., 2022). Overall, H3L represents a significant target for both prophylactic and therapeutic interventions against poxvirus-related diseases.

Other names

Ag35Virion envelope protein p35p35OPG108H3

Neutralizing antibodies bind to H3L to block viral adsorption to cell surface heparan sulfate and inhibit the maturation of intracellular mature virions.