One of the most important steps of virus entry into host cells is the virus-cell membrane fusion. Enveloped viruses could be classified into three types according to the different mechanisms enveloped virus realizes cell entry. The type I and II require only a single glycoprotein for membrane fusion. However, the type III involves several enveloped proteins to complete the fusion process which is complicated and few about the mechanisms are known currently.

In order to revealing this process, researchers in Professor George F Gao’s lab  at the Institute of Microbiology, Chinese Academy of Sciences determined the complex structure of HSV-1 gD bound to nectin-1, with the method of x-ray crystallography.

Herpes Simplex Virus (HSV) is a typical type III enveloped virus. Revealing the interaction mode between HSV glycoproteins and their receptors will contribute to the understanding of the entry mechanism of type III enveloped virus and thereby facilitate the development of small molecules to inhibit HSV entry into host cells. HSV entry is a multi-event requiring cooperative interaction of viral enveloped protein/s with host surface receptor/s. During this process, glycoprotein D (gD) plays an important role by binding to the host receptors such as nectin-1. Nevertheless, the detailed interaction between gD and nectin-1 remains elusive to date. Their finding reveals that gD binds the first Ig domain of nectin-1 in a similar mode to the nectin-1 homodimer interaction. This unique binding mode precludes the nectin-1 dimerization, consequently abolishing its cell adhesion function. The determination of the complex structure reveals a mechanism on the exploitation of host molecules by HSV for its own sake.

This work has been published in Nature Communations 2011,2:557 (doi: 10.1038/ ncomms 1571). This project was supported by the National Program on Key Basic Research Project of China (973 Program) of the Ministry of Science and Technology of China.