Herpes simplex virus type 2 glycoprotein G (gG-2)

Herpes simplex virus type 2 glycoprotein G (gG‑2) is an envelope glycoprotein encoded by HSV‑2 that undergoes unusual post‑translational cleavage into a secreted N‑terminal fragment (SgG2) and a heavily O‑glycosylated C‑terminal fragment that remains associated with the virion envelope and infected cell membrane. Mature gG‑2 is a major target of the human antibody response and provides highly type‑specific epitopes, making it an excellent antigen for serologic tests that distinguish HSV‑2 from HSV‑1 infection. Functionally, gG‑2 is a multifunctional component of the viral envelope: it binds sulfated oligo- and polysaccharides and is targeted by inhibitors such as PI‑88 and heparin during early infection, and it promotes efficient egress and release of infectious virus from infected cells. The secreted form SgG2 binds chemokines with high affinity and, unlike most viral chemokine-binding proteins, enhances chemokine function, thereby modulating immune cell recruitment. SgG2 also binds nerve growth factor (NGF) with high affinity, alters NGF–TrkA receptor signaling by redistributing TrkA in lipid rafts and reducing its internalization and retrograde transport, and enhances NGF‑dependent axonal growth in sensory neurons and skin, potentially facilitating HSV‑2 infection of peripheral nerve endings and neural invasion. Clinical HSV‑2 isolates that are gG‑2‑negative have been described and carry frameshift and other mutations in the gG‑2 gene, indicating that gG‑2, while immunologically and functionally important, is not absolutely essential for viral replication in vitro.

Other names

Herpes simplex virus 2 glycoprotein GHSV-2 glycoprotein GGlycoprotein G-2gG2Secreted glycoprotein G-2 (SgG2)Mature glycoprotein G-2 (mgG-2)

Sulfated oligo- and polysaccharide inhibitors (e.g., PI‑88, heparin) bind to HSV‑2 gG and other envelope glycoproteins, blocking or reducing initial virus–cell interactions and attachment, thereby inhibiting early stages of infection. Antiviral inhibition can be reduced or bypassed when viruses lack gG expression, indicating that gG-2 is one of the targets through which these entry inhibitors act.