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Second-site suppressors of Rous sarcoma virus Ca mutations: evidence for interdomain interactions
J B Bowzard1, J W Wills, R C Craven
1Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, M. S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA.
Journal of Virology
|July 4, 2001
Summary
Mutations in the major homology region (MHR) of capsid (CA) proteins are lethal, disrupting retroviral replication. Suppressors reveal communication between CA domains, impacting viral assembly and maturation.
Area of Science:
- Virology
- Molecular Biology
- Structural Biology
Background:
- The capsid (CA) protein is crucial for retroviral structure and replication, forming a shell around the genetic material.
- The major homology region (MHR) within CA is highly conserved and implicated in replication processes common to retroviruses and related elements.
Purpose of the Study:
- To investigate the function of the MHR in retroviral replication.
- To identify genetic suppressors of lethal MHR mutations and elucidate their mechanisms of action.
Main Methods:
- Introduction of lethal mutations into the MHR of Rous sarcoma virus CA protein.
- Genetic screening to identify suppressor mutations.
- Analysis of suppressor mutations' effects on viral replication, particle assembly, and maturation.
Main Results:
- Conservative MHR substitutions were lethal, causing severe reverse transcription deficiencies.
- Four suppressors of lethal MHR mutations were identified, all mapping to the CA-spacer peptide (SP) region.
- One suppressor restored function by correcting dimerization defects, while another enhanced SP cleavage, modifying the maturation pathway.
- Suppressors of other MHR mutations mapped to the N-terminal CA domain, suggesting inter-domain communication.
Conclusions:
- The MHR is essential for proper retroviral replication, likely through interactions with other viral components.
- Suppressor mutations highlight the importance of CA dimerization, maturation, and inter-domain communication in the viral life cycle.
- The findings suggest a coordinated interplay between different regions of the CA protein during viral replication.
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