Structural and functional characterization of EIAV gp45 fusion peptide proximal region and asparagine-rich layer

• The crystal structure of EIAV gp45 was determined.
• The fusion peptide proximal region adopts a novel conformation different to HIV-1.
• The asparagine-rich layer includes an extensive hydrogen-bond network.
• These regions of EIAV are highly tolerant to mutations.
• The results provide insight into the mechanism of gp41/gp45-mediated membrane fusion.

Equine infectious anaemia virus (EIAV) and human immunodeficiency virus (HIV) are members of the lentiviral genus. Similar to HIV gp41, EIAV gp45 is a fusogenic protein that mediates fusion between the viral particle and the host cell membrane. The crystal structure of gp45 reported reveals a different conformation in the here that includes the fusion peptide proximal region (FPPR) and neighboring asparagine-rich layer compared with previous HIV-1 gp41 structures. A complicated hydrogen-bond network containing a cluster of solvent molecules appears to be critical for the stability of the gp45 helical bundle. Interestingly, viral replication was relatively unaffected by site-directed mutagenesis of EIAV, in striking contrast to that of HIV-1. Based on these observations, we speculate that EIAV is more adaptable to emergent mutations, which might be important for the evolution of EIAV as a quasi-species, and could potentially contribute to the success of the EIAV vaccine.