Segmented RNA viruses are important pathogens of humans, animals and plants. An understanding of how these viruses replicate and evolve during their spread in nature is expected to inform disease treatment and prevention strategies.
A shared feature of all segmented RNA viruses is their capacity to exchange genome segments during co-infection by a process called reassortment. Specifically, when two or more viruses infect a single host cell, they can each package genome segments from the other virus into a nascent hybrid virion.
Several factors constrain the generation of reassortants during co-infection, including incompatible RNA–RNA interactions between different gene segments, and incompatible protein–RNA interactions between molecules from different viral strains.
Multiple selection pressures can promote or prevent the emergence of reassortant viruses in the population. For example, reassortment can increase viral fitness by enabling the reassortant to escape immune recognition, but it can also decrease viral fitness by uncoupling essential cognate protein sets that interact optimally when kept together.
Segmented RNA viruses are widespread in nature and include important human, animal and plant pathogens, such as influenza viruses and rotaviruses. Although the origin of RNA virus genome segmentation remains elusive, a major consequence of this genome structure is the capacity for reassortment to occur during co-infection, whereby segments are exchanged among different viral strains. Therefore, reassortment can create viral progeny that contain genes that are derived from more than one parent, potentially conferring important fitness advantages or disadvantages to the progeny virus. However, for segmented RNA viruses that package their multiple genome segments into a single virion particle, reassortment also requires genetic compatibility between parental strains, which occurs in the form of conserved packaging signals, and the maintenance of RNA and protein interactions. In this Review, we discuss recent studies that examined the mechanisms and outcomes of reassortment for three well-studied viral families — Cystoviridae, Orthomyxoviridae and Reoviridae — and discuss how these findings provide new perspectives on the replication and evolution of segmented RNA viruses.
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S.M.M. receives financial support from the Virginia Tech Carilion School of Medicine and Research Institute and the US National Institutes of Health (NIH; grants R01AI116815, R21AI113402 and R21AI119588). P.E.T. receives financial support from the US National Science Foundation BEACON Center for Study of Evolution in Action and the NIH (grant R01AI09164601). J.T.P. is supported by funding from the University of Maryland, College Park, USA.
The authors declare no competing financial interests.
- Segmented RNA viruses
Viruses in which the genome consists of more than one RNA molecule (that is, segments). The genome segments can be packaged within a single virion particle or into separate particles.
- Type species
A representative viral strain that is studied to understand the biology of an entire viral genus or family.
A process of genetic exchange whereby two or more parental viruses co-infect a single host cell and exchange genome segments. The outcome is the formation of hybrid viral progeny with genome segments derived from multiple parental strains.
The mechanism by which a segmented virus packages one of each genome segment into a virion particle.
- Viral fitness
The capacity of an individual virus to generate infectious progeny, relative to other virus genotypes in the population.
Bacterial strains with the same or similar characteristics.
- In vitro packaging system
A simplified experimental system in which viral genome segments are incorporated into a virion particle; this occurs in a test tube and outside the context of an infected host cell.
- Defective-interfering RNAs
Spontaneously generated mutant RNA molecules that usually contain large gene deletions but maintain sequences that are crucial for their replication and packaging. These RNAs reduce the fitness of full-length viruses during cellular co-infection.
- HA–NA subtype
A binomial system of classification for influenza A viruses that is based on the neutralizing antibody response to the virion structural proteins haemagglutinin (HA) and neuraminidase (NA).
- Diploidy or polyploidy
In virology: when an individual virus encapsidates two (diploidy) or more (polyploidy) copies of the genome into a single virus particle.
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McDonald, S., Nelson, M., Turner, P. et al. Reassortment in segmented RNA viruses: mechanisms and outcomes. Nat Rev Microbiol 14, 448–460 (2016). https://doi.org/10.1038/nrmicro.2016.46
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