Antigenic and structural insights into Langya henipavirus attachment glycoprotein

Area of Science:

• Virology
• Structural Biology
• Immunology

Background:

• Langya henipavirus (LayV), a novel henipavirus, emerged in China in 2022.
• Henipavirus entry into host cells involves interactions between viral glycoproteins (G and F) and cellular receptors.
• LayV shares high amino acid homology (86%) in its G protein with Mojiang virus (MojV), forming a unique evolutionary clade.

Purpose of the Study:

• To elucidate the structural characteristics of the Langya henipavirus G protein.
• To investigate the binding capabilities of the LayV G protein with known henipavirus receptors and antibodies.
• To assess the immunogenicity and cross-reactivity of antibodies generated against the LayV G protein.

Main Methods:

• Crystal structure determination of the LayV G protein at 3.4 Å resolution.
• Analysis of LayV G protein's structural features, including domain organization and glycosylation.
• Binding assays to test interactions with ephrin B2 receptors and existing henipavirus-neutralizing antibodies.
• Immunogenicity studies in mice to evaluate antibody responses and cross-reactivity against related henipaviruses.

Main Results:

• The LayV G protein structure features a head domain with six β-propeller-like domains and lacks glycosylation, distinguishing it from NiV and HeV G proteins.
• A prominent central loop creates unique structural features within the LayV G protein's cavity.
• LayV G protein did not bind to ephrin B2 receptors or established henipavirus-neutralizing antibodies.
• Immunization with LayV G protein induced robust antibody responses in mice, with strong reactivity against LayV and MojV G proteins, but weak cross-reactivity against other henipaviruses.

Conclusions:

• The unique structural and binding properties of the LayV G protein necessitate specific diagnostic and therapeutic strategies.
• The limited cross-reactivity of induced antibodies highlights the need for tailored vaccines against LayV and related novel henipaviruses.
• Understanding LayV G protein's distinct characteristics is crucial for developing effective countermeasures against emerging henipaviruses.