Biologically Relevant, Cationic Residues in Human Rhinovirus Stabilize Capsid-Bound RNA Duplexes, and Restrict Capsid...

Area of Science:

• Structural biology
• Virology
• Biochemistry

Background:

• Human rhinoviruses (RV) cause significant health and economic burdens, yet lack specific antiviral treatments.
• Capsid-RNA interactions are crucial for RV assembly and infection, with specific charged residues like K4058 and K2052 playing key roles.
• Previous research identified an RNA dodecahedral cage within the RV-B14 virion stabilized by intrachain RNA duplexes.

Purpose of the Study:

• To investigate the structural basis of positively charged residues' (K4058, K2052) functional roles in RV virions.
• To understand how these residues modulate capsid conformation and RNA organization.
• To explore the implications for RV assembly, genome uncoating, and potential antiviral drug development.

Main Methods:

• Cryogenic electron microscopy (cryo-EM) was employed to determine high-resolution structures.
• Atomic structures of mutant RV-B14 virions (K4058A, K2052A) were compared to the parental wild-type.
• Equilibrium conformation dynamics were analyzed under identical conditions.

Main Results:

• Both K4058 and K2052 residues were found to stabilize the internal RNA duplex structures within the virion.
• These residues modulate the capsid's conformation and influence its equilibrium dynamics.
• Mutant virions showed partially disorganized RNA, resembling alternative wild-type structures, suggesting conformational flexibility.

Conclusions:

• The study reveals that specific capsid residues (K4058, K2052) are critical for maintaining the structural integrity of the viral RNA.
• RV virions can exist in at least two conformational states: a basal state with structured RNA and an activated state with disorganized RNA, influencing RNA release.
• These findings provide insights into RV structural dynamics and potential targets for antiviral therapies.