Structure-Based Classification Defines the Discrete Conformational Classes Adopted by the Arenaviral GP1

Area of Science:

• Virology
• Structural Biology
• Immunology

Background:

• Arenaviruses, emerging from rodent reservoirs, pose a significant threat to human health.
• The GP1 subunit of the arenaviral glycoprotein spike complex (GPC) is vital for host cell recognition and cross-species transmission.
• Previous studies indicated GP1 glycoproteins adopt distinct conformational states.

Purpose of the Study:

• To investigate the conformational states of Old and New World arenaviral GP1 glycoproteins.
• To determine if conformational rearrangements in GP1 are specific to Old World arenaviruses and independent of pH.
• To provide a structure-based phylogenetic analysis of arenaviral GP1s.

Main Methods:

• Comparative structural analysis of Old World Loei River virus and New World Whitewater Arroyo virus GP1.
• Structure-based phylogenetic analysis of arenaviral GP1 glycoproteins.

Main Results:

• Conformational rearrangements in GP1 are restricted to Old World arenaviruses.
• These structural changes are not solely induced by pH changes associated with endosomal trafficking.
• GP1 from Old World arenaviruses adopts a distinct, pH-independent conformation absent GP2.

Conclusions:

• Arenaviral GP1 conformations are phylogenetically distinct between Old and New World viruses.
• Understanding these discrete structural classes is key for therapeutic target development.
• This research informs strategies for creating arenaviral glycoprotein immunogens for vaccine development.