Simultaneous membrane and RNA binding by tick-borne encephalitis virus capsid protein

Area of Science:

• Virology
• Molecular Biology
• Biophysics

Background:

• Tick-borne encephalitis virus (TBEV) is a pathogenic flavivirus responsible for severe neurological disease.
• Viral particle formation involves nucleocapsid budding through the endoplasmic reticulum membrane.
• The precise mechanisms coordinating nucleocapsid assembly and membrane budding remain unclear.

Purpose of the Study:

• To investigate the interactions between TBEV capsid proteins and membranes.
• To elucidate the role of capsid proteins in nucleocapsid assembly and viral budding.
• To understand the contribution of membrane lipids in TBEV replication.

Main Methods:

• Biophysical methods were employed to study wild-type and truncated capsid proteins.
• Model membrane systems were utilized to mimic endoplasmic reticulum membrane environments.
• Mass spectrometry was used to analyze the lipid composition of purified TBEV virions.

Main Results:

• Capsid proteins initially bind to membranes via electrostatic interactions with negatively-charged lipids.
• Membrane-bound capsid proteins facilitate the insertion into the membrane.
• Capsid proteins recruit viral genomic RNA to the membrane, and virions contain negatively-charged lipids.

Conclusions:

• Negatively-charged membrane patches on the endoplasmic reticulum likely coordinate TBEV nucleocapsid assembly.
• The capsid protein acts as a crucial mediator for direct interactions between the nucleocapsid and the host cell membrane.
• These findings provide insights into the early stages of flavivirus particle formation.