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The P gene of bovine parainfluenza virus 3 expresses all three reading frames from a single mRNA editing site
T Pelet1, J Curran, D Kolakofsky
1Department of Microbiology, University of Geneva Medical School, Switzerland.
Abstract:
The P gene of bovine parainfluenza virus 3 (bPIV3) contains two downstream overlapping ORFs, called V and D. By comparison with the mRNA editing sites of other paramyxoviruses, two editing sites were predicted for bPIV3; site a to express the D protein, and site b to express the V protein. Examination of the bPIV3 mRNAs, however, indicates that site b is non-functional whereas site a operates frequently. Insertions at site a give rise to both V and D protein mRNAs, because a very broad distribution of Gs is added when insertions occur. This broad distribution is very different from the editing sites of Sendai virus or SV5, where predominantly one form of edited mRNA containing either a one or two G insertion respectively is created, to access the single overlapping ORF of these viruses. A model is proposed to explain how paramyxoviruses control the range of G insertions on that fraction of the mRNAs where insertions occur. The bPIV3 P gene is unique as far as we know, in that a sizeable portion of the gene expresses all 3 reading frames as protein. bPIV3 apparently does this from a single editing site by removing the constraints which control the number of slippage rounds which take place.
Insights
Bovine parainfluenza virus 3 (bPIV3) utilizes a unique mRNA editing site to express V and D proteins from its P gene. Unlike other paramyxoviruses, bPIV3 achieves this by allowing a broad range of G insertions at a single site.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- The P gene of bovine parainfluenza virus 3 (bPIV3) encodes two downstream overlapping open reading frames (ORFs): V and D.
- Paramyxoviruses commonly use mRNA editing to generate multiple proteins from a single gene.
- Previous studies predicted two editing sites (a and b) in bPIV3 for expressing D and V proteins, respectively.
Purpose of the Study:
- To investigate the functionality of predicted mRNA editing sites in the bPIV3 P gene.
- To understand the mechanism of V and D protein expression in bPIV3.
- To compare bPIV3 mRNA editing with that of other paramyxoviruses.
Main Methods:
- Analysis of bPIV3 mRNAs to identify functional editing sites.
- Comparison of bPIV3 editing patterns with those of Sendai virus and SV5.
- Development of a model to explain G insertion control during paramyxovirus mRNA editing.
Main Results:
- Site b for V protein expression was found to be non-functional.
- Site a frequently operates, leading to the expression of both V and D proteins.
- bPIV3 exhibits a broad distribution of G insertions at site a, unlike the restricted insertions in Sendai virus or SV5.
- The P gene of bPIV3 uniquely expresses proteins from all three reading frames from a single editing site.
Conclusions:
- bPIV3 employs a single, highly active editing site (site a) to produce both V and D proteins.
- The virus achieves this by removing constraints on G insertion, allowing a wide range of additions.
- This mechanism allows bPIV3 to express proteins from all three reading frames of the P gene, a unique characteristic among known paramyxoviruses.