Stuck in the middle: structural insights into the role of the gH/gL heterodimer in herpesvirus entry.

Enveloped viruses enter cells by fusing the viral and cellular membranes, and most use a single viral envelope protein that combines receptor-binding and fusogenic functions. In herpesviruses, these functions are distributed among multiple proteins: the conserved fusion protein gB, various non-conserved receptor-binding proteins, and the conserved gH/gL heterodimer that curiously lacks an apparent counterpart in other enveloped viruses. Recent structural studies of gH/gL from HSV-2 and EBV revealed a unique complex with no structural or functional similarity to other viral proteins. Here we analyzed gH/gL structures and highlighted important functional regions. We propose that gH/gL functions as an adaptor that transmits the triggering signals from various non-conserved inputs to the highly conserved fusion protein gB.