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Towards an integrative view of virus phenotypes

Abstract

Understanding how phenotypes emerge from genotypes is a foundational goal in biology. As challenging as this task is when considering cellular life, it is further complicated in the case of viruses. During replication, a virus as a discrete entity (the virion) disappears and manifests itself as a metabolic amalgam between the virus and the host (the virocell). Identifying traits that unambiguously constitute a virus’s phenotype is straightforward for the virion, less so for the virocell. Here, we present a framework for categorizing virus phenotypes that encompasses both virion and virocell stages and considers functional and performance traits of viruses in the context of fitness. Such an integrated view of virus phenotype is necessary for comprehensive interpretation of viral genome sequences and will advance our understanding of viral evolution and ecology.

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Fig. 1: Phenotypes and traits during the virus life cycle.
Fig. 2: How the performance trait of burst size may arise from the interactions of multiple functional traits and the environment.
Fig. 3: Phenotypic plasticity of a virus due to temperature.
Fig. 4: Reproduction strategies and pathways of replication inside host cells.

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Acknowledgements

This Review was inspired by discussions at a workshop supported by the US National Science Foundation under grant no. 1736030, and by the Delaware INBRE programme, with a grant from the US National Institute of General Medical Sciences (P20 GM103446) from the US National Institutes of Health and the State of Delaware.

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Z.T.A.-A., M.A.A.-S., D.D.D., J.P.D., K.F.E., B.D.F., J.J.F., J.P.G., A.O.H., K.H., H.L., M.F.M., R.M.M., S.W.P., M.E.S., J.S. and K.E.W. researched data for the article, D.D.D., J.P.D., K.F.E., J.P.G., M.F.M., C.R.S. and K.E.W. contributed substantially to discussion of the content, D.D.D., J.P.D., K.F.E., J.J.F., J.P.G., M.F.M., S.W.P., C.R.S., G.F.S., J.L.V.E. and K.E.W. wrote the manuscript and D.D.D., J.P.D., K.F.E., J.J.F., J.P.G., M.F.M., S.W.P., C.R.S. and K.E.W. reviewed or edited the manuscript before submission.

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Correspondence to John P. DeLong or K. Eric Wommack.

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Nature Reviews Microbiology thanks H. Ogata, who co-reviewed with H. Endo, S. Roux and the other, anonymous, reviewer for their contribution to the peer review of this work.

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Glossary

Reassortment

When genome segments from different infecting viruses combine to form a new viral genome.

Episome

A length of viral genome occurring within a host cell.

T number

The number of sides of a virion.

Segmented

A genome separated into different parts and not physically connected.

Monopartite

Referring to a virus with a non-segmented genome.

Bipartite

Referring to a virus with a genome segmented into two parts.

Multiplicity of infection

The ratio of infecting viruses to hosts.

G+C content

The proportion of all the nucleotides that are guanine or cytosine.

Interferons

Host proteins that can inhibit virus reproduction.

Restriction–modification systems

A tool for breaking up foreign DNA within host cells.

CRISPR–Cas immunity

Genetic sequences that can be used to identify and destroy foreign genomes.

Plasmodesmata

Cytoplasmic connections between neighbouring plant cells.

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DeLong, J.P., Al-Sammak, M.A., Al-Ameeli, Z.T. et al. Towards an integrative view of virus phenotypes. Nat Rev Microbiol (2021). https://doi.org/10.1038/s41579-021-00612-w

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