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  • Review Article
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Viral and host heterogeneity and their effects on the viral life cycle

Nature Reviews Microbiology volume 19, pages 272–282 (2021)Cite this article

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Abstract

Traditionally, the viral replication cycle is envisioned as a single, well-defined loop with four major steps: attachment and entry into a target cell, replication of the viral genome, maturation of viral proteins and genome packaging into infectious progeny, and egress and dissemination to the next target cell. However, for many viruses, a growing body of evidence points towards extreme heterogeneity in each of these steps. In this Review, we reassess the major steps of the viral replication cycle by highlighting recent advances that show considerable variability during viral infection. First, we discuss heterogeneity in entry receptors, followed by a discussion on error-prone and low-fidelity polymerases and their impact on viral diversity. Next, we cover the implications of heterogeneity in genome packaging and assembly on virion morphology. Last, we explore alternative egress mechanisms, including tunnelling nanotubes and host microvesicles. In summary, we discuss the implications of viral phenotypic, morphological and genetic heterogeneity on pathogenesis and medicine. This Review highlights common themes and unique features that give nuance to the viral replication cycle.

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Fig. 1: Heterogeneity in the virus replication cycle.
Fig. 2: Heterogeneity in glycosylation of entry receptors.
Fig. 3: Heterogeneity in influenza virus particle morphology.

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Acknowledgements

The authors thank members of the Lakdawala laboratory for critical reading of this review. S.S.L. is funded by National Institutes of Health (NIH) grant (1R01AI139063-01A1), the American Lung Association Biomedical Research grant and a New Initiative Award from the Charles E. Kaufman Foundation, a supporting organization of The Pittsburgh Foundation. J.E.J. is a recipient of a Catalyst Award from the University of Pittsburgh Center for Evolutionary Biology and Medicine and a T32 (T32 AI049820) from the University of Pittsburgh.

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Authors and Affiliations

  1. Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Jennifer E. Jones, Valerie Le Sage & Seema S. Lakdawala

  2. Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Seema S. Lakdawala

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  1. Jennifer E. Jones
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  2. Valerie Le Sage
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All authors researched data for the article and contributed to discussion of the content. J.E.J., V.L. and S.S.L wrote the article. All authors reviewed and edited the manuscript before submission.

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Correspondence to Seema S. Lakdawala.

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Nature Reviews Microbiology thanks N. Altan-Bonnet and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Pleomorphic viruses

A population of viruses exhibiting irregularity of size, shape or protein copy number.

Receptor avidity

The strength or affinity of the interaction between a viral receptor-binding protein and its target ligand on a host cell.

Multiplicity of infection

The ratio of the number of infectious units of a virus to the number of cells.

Epistatic mutations

Mutations whose effects are dependent upon the presence or absence of one or more mutations in other genes.

Plaque-forming unit

(PFU). The concentration of viruses capable of lysing host cells and forming a visible plaque, per unit volume.

Syncytia

A multinucleate cell arising from fusion of several cells.

Minimal infectious unit

The minimal concentration of virus particles required to initiate infection.

Exosomes

Extracellular vesicles produced in the host cell carrying proteins and RNA that are released into the extracellular space and can fuse with neighbouring cells.

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Jones, J.E., Le Sage, V. & Lakdawala, S.S. Viral and host heterogeneity and their effects on the viral life cycle. Nat Rev Microbiol 19, 272–282 (2021). https://doi.org/10.1038/s41579-020-00449-9

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