Crystal structure of the conserved herpesvirus fusion regulator complex gH–gL

Herpesviruses, which cause many incurable diseases, infect cells by fusing viral and cellular membranes. While most other enveloped viruses use a single viral catalyst, called a fusogen, herpesviruses, inexplicably, require two conserved fusion-machinery components, gB and the heterodimer gH–gL, plus other non-conserved components. gB is a class III viral fusogen but, unlike other members of its class, does not function alone. We determined the crystal structure of the gH ectodomain bound to gL, from herpes simplex virus 2. gH–gL is an unusually tight complex of a novel architecture that, unexpectedly, does not resemble any known viral fusogen. Instead, we propose that gH–gL activates gB for fusion, possibly through direct binding. Formation of a gB–gH–gL complex is critical for fusion and is inhibited by a neutralizing antibody, making gB–gH–gL interface a promising antiviral target.