Herpes glycoprotein gL is distantly related to chemokine receptor ligands

Glycoprotein L (gL) is one of the critical proteins involved in transmission of Herpesviridae. We applied the methodology of protein structure prediction to shed a light on the so far unknown molecular mechanism of its action. Here we show that gL forms a chemokine-like protein. Alphaherpesvirinae gL as well as CMV functional homolog (UL130) create a novel CX chemokine-like protein, while Gammaherpesvirinae gL (HHV8 and EBV) adopt a regular CC beta-chemokine fold.We conclude that gL may interact with specific cellular chemokine receptors during the invasion of Herpesviridae. The proposed mechanism has a potential impact on future development of novel therapeutic and prophylactic strategies.