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Updated: Jul 4, 2026
11:48
Generation, Amplification, and Titration of Recombinant Respiratory Syncytial Viruses
Published on: April 4, 2019
The cis-acting replication elements define human enterovirus and rhinovirus species
Samuel Cordey1, Daniel Gerlach, Thomas Junier
1Central Laboratory of Virology, Division of Infectious Diseases, University of Geneva Hospitals, 1211 Geneva 14, Switzerland. samuel.cordey@hcuge.ch
RNA (New York, N.Y.)
|June 11, 2008
Summary
Picornavirus replication relies on cis-acting replication elements (cre). This study identifies a novel cre in HRV-A2 and demonstrates that HRV-B cre is nonfunctional, suggesting cre elements are key to HRV and HEV evolution and classification.
Area of Science:
- Virology
- Molecular Biology
- Evolutionary Biology
Background:
- Picornavirus replication is dependent on VPg uridylylation, a process linked to cis-acting replication elements (cre).
- Cre elements are located within the polyprotein-encoding sequence at distinct positions across different picornavirus species.
- Previous studies identified cre in poliovirus, coxsackievirus-B3, cardiovirus, and human rhinovirus (HRV) types A and B, overlapping various proteins.
Purpose of the Study:
- To report a novel cre element in the VP2 region of HRV-A2 and provide evolutionary evidence for its function.
- To experimentally assess the functionality of the HRV-B cre in the 2C region, orthologous to human enterovirus (HEV) cre.
- To investigate the role of specific amino acids in the 2C protein for viral replication.
Main Methods:
- Identification and characterization of a novel cre element in HRV-A2.
- Experimental interrogation of HRV-B cre functionality.
- Mutational analysis of the 2C protein.
- Evolutionary analysis of cre elements across HRV and HEV clades.
Main Results:
- A novel, functional cre element was identified in the VP2 region of HRV-A2.
- The identified HRV-B cre in the 2C region was found to be dispensable for replication, suggesting it is a nonfunctional relic.
- Mutational analysis revealed two crucial amino acids in the 2C protein essential for viral replication.
- Each genetic clade of HRV and HEV is characterized by a unique functional cre element.
Conclusions:
- The cre element is a defining feature that evolves with new genetic lineages of HRV and HEV.
- The study proposes that cre elements can serve as an additional criterion for the classification of human rhinoviruses and enteroviruses.
- Functional cre elements are critical for viral evolutionary success, with novel motifs emerging and ancestral ones decaying.
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