The μ1 72-96 loop controls conformational transitions during reovirus cell entry

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• The reovirus outer capsid protein μ1 is crucial for viral stability and cell entry.
• μ1 undergoes conformational changes during cell entry to deliver the viral core.
• The 72-96 loop of μ1 is proposed to stabilize the capsid through inter-trimer and trimer-core interactions.

Purpose of the Study:

• To investigate how μ1's capsid-stabilizing functions affect its conformational changes during cell entry.
• To characterize the impact of mutations in the μ1 72-96 loop on reovirus replication and cell entry.

Main Methods:

• Site-directed mutagenesis of charged residues within the μ1 72-96 loop.
• Characterization of mutant viruses, including replication efficiency and conversion of infectious subvirion particles (ISVPs) to ISVP*s.
• Analysis of second-site revertants to identify compensatory mutations.

Main Results:

• Mutations at Glu89 (E89) in the μ1 72-96 loop compromised viral replication.
• E89 mutants showed enhanced, unregulated conversion of ISVPs to ISVP*s.
• Revertants with second-site mutations restored viral fitness and regulated ISVP-to-ISVP* conversion.

Conclusions:

• Specific regions of μ1 are critical for stabilizing the reovirus capsid.
• Unregulated conformational changes of μ1, leading to premature ISVP* formation, compromise viral fitness.
• Balancing capsid stability and regulated conformational change is essential for reovirus replication.