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Polyploid measles virus with hexameric genome length
Monika Rager1, Sompong Vongpunsawad, William Paul Duprex
1Molecular Medicine Program, Mayo Clinic, Guggenheim 1838, 200 First Street SW, Rochester, MN 55905, USA.
Abstract:
Particles of most virus species accurately package a single genome, but there are indications that the pleomorphic particles of parainfluenza viruses incorporate multiple genomes. We characterized a stable measles virus mutant that efficiently packages at least two genomes. The first genome is recombinant and codes for a defective attachment protein with an appended domain interfering with fusion-support function. The second has one adenosine insertion in a purine run that interrupts translation of the appended domain and restores function. In that genome, a one base deletion in a different purine run abolishes polymerase synthesis, but restores hexameric genome length, thus ensuring accurate RNA encapsidation, which is necessary for efficient replication. Thus, the two genomes are complementary. The infection kinetics of this mutant indicate that packaging of multiple genomes does not negatively affect growth. We also show that polyploid particles are produced in standard infections at no expense to infectivity. Our results illustrate how the particles of parainfluenza viruses efficiently accommodate cargoes of different volume, and suggest a mechanism by which segmented genomes may have evolved.
Insights
Measles virus mutants can package multiple genomes, with complementary RNA genomes ensuring efficient replication. Polyploid virus particles are produced without impacting infectivity or growth.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Most viruses package a single genome, but parainfluenza viruses may package multiple genomes.
- Measles virus (a paramyxovirus) typically has a single-stranded RNA genome.
Purpose of the Study:
- To characterize a measles virus mutant that packages multiple genomes.
- To investigate the functional implications of polyploid viral particles.
Main Methods:
- Characterization of a stable measles virus mutant with multiple genomes.
- Analysis of RNA sequences, translation, and polymerase activity.
- Assessment of infection kinetics and particle infectivity.
Main Results:
- A measles virus mutant was identified that packages at least two complementary RNA genomes.
- One genome contained mutations restoring attachment protein function and ensuring accurate RNA encapsidation.
- Polyploid particles were produced in standard infections without compromising viral growth or infectivity.
Conclusions:
- Measles virus particles can efficiently accommodate multiple RNA genomes of varying sizes.
- This packaging mechanism suggests a pathway for the evolution of segmented viral genomes.