Envelope glycoprotein C (HSV-2) (gC2)

HSV-2 glycoprotein gC2 (gC2) is a critical type 1 transmembrane glycoprotein found on the envelope of Herpes Simplex Virus type 2 (UniProt, 2026). It serves two primary functions: mediating the initial attachment of the virus to host cells by binding to heparan sulfate proteoglycans and acting as an immune evasion molecule by binding to host complement component C3b (Awasthi et al., 2014). By sequestering C3b, gC2 inhibits the activation of the complement cascade, which would otherwise lead to virus neutralization and the lysis of infected cells (Friedman et al., 2021). This immune-shielding effect is further enhanced through synergy with glycoprotein E (gE2), which blocks IgG Fc-mediated activities (Hook et al., 2019). Because of these roles, gC2 has become a key component in the development of multivalent vaccines, such as the trivalent mRNA-LNP vaccine BNT163 and mRNA-1608, which aim to elicit antibodies that both block viral entry and prevent immune evasion (BioNTech, 2022; Moderna, 2023). Therapeutic strategies targeting gC2 are designed to restore the efficacy of the host's innate and adaptive immune responses against the virus (Awasthi et al., 2014). These vaccines have shown promise in preclinical models by significantly reducing viral shedding and protecting against neuroinvasion (Hook et al., 2019). Overall, gC2 represents a high-value target for preventing both the clinical symptoms and the transmission of genital herpes (Friedman et al., 2021).

Other names

Glycoprotein CgC-2UL44Envelope glycoprotein C

Vaccines and experimental antibodies targeting gC2 work by blocking its ability to bind host complement component C3b, thereby preventing the virus from evading the complement-mediated immune response, and by interfering with the initial attachment of the virus to host cell heparan sulfate receptors.