Structure and antigenicity of divergent Henipavirus fusion glycoproteins

 The novel Henipavirus (HNV), Langya virus (LayV) was found in China, caused severe pneumonic disease in human. The discovery of LayV that causes infection in human beside Nipah virus (NiV) and Hendra virus (HeV), highlights the emergence of HNVs threat to global health. Despite the significant mortality and morbidity, there are currently no licensed vaccines or treatment for HNVs. This study was performed to identify the prefusion structures of Mòjiāng virus (MojV) and LayV fusion (F) proteins using cryogenic electron microscopy. The results showed that LayV and MojV F have a similar structure with NiV F, indicating the tendency of RNA viruses that prone to significant rates of mutation while maintaining overall structure for functionality. This study discovered that prefusion NiV F polyclonal sera had minimal to no cross-reactivity with MojV and LayV F, which has significance for the development of broad-spectrum vaccines. The HNV F glycoproteins possess higher sequence conservation in comparison to HNV G glycoproteins, indicating that F glycoprotein may be a better candidate for a broad-spectrum vaccine. Glycoproteomic analysis showed a significant less glycosylation of F protein in LayV, however, LayV F contains a glycan that protect a susceptible site in NiV. Despite being structurally similar with NiV, LayV and MojV F have a significant difference in the antigenic profile. The lack of glycans on the main surface of glycoproteins may translate into higher susceptibility to antibody neutralization, which may have consequences for vaccine and treatment design.

(MA)