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  • Review Article
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The human virome: assembly, composition and host interactions

Abstract

The human body hosts vast microbial communities, termed the microbiome. Less well known is the fact that the human body also hosts vast numbers of different viruses, collectively termed the ‘virome’. Viruses are believed to be the most abundant and diverse biological entities on our planet, with an estimated 1031 particles on Earth. The human virome is similarly vast and complex, consisting of approximately 1013 particles per human individual, with great heterogeneity. In recent years, studies of the human virome using metagenomic sequencing and other methods have clarified aspects of human virome diversity at different body sites, the relationships to disease states and mechanisms of establishment of the human virome during early life. Despite increasing focus, it remains the case that the majority of sequence data in a typical virome study remain unidentified, highlighting the extent of unexplored viral ‘dark matter’. Nevertheless, it is now clear that viral community states can be associated with adverse outcomes for the human host, whereas other states are characteristic of health. In this Review, we provide an overview of research on the human virome and highlight outstanding recent studies that explore the assembly, composition and dynamics of the human virome as well as host–virome interactions in health and disease.

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Fig. 1: Phage replication cycles.
Fig. 2: The human virome at different body sites.
Fig. 3: Stepwise assembly of the paediatric virome.
Fig. 4: Factors that shape the human virome.
Fig. 5: Host–virome interactions.

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Acknowledgements

The authors thank members of the Bushman laboratory for help and suggestions, and L. Zimmerman for artwork designs. This work was supported by the National Institutes of Health (NIH) (grants R61-HL137063, R01-HL113252), the Penn Center for AIDS Research (P30 AI 045008), the PennCHOP Microbiome Program and a Tobacco Formula grant under the Commonwealth Universal Research Enhancement (CURE) programme (grant number SAP # 4100068710), and the Crohn’s and Colitis Foundation.

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Glossary

Temperate phages

Phages that are able to grow via both lytic and lysogenic replication pathways.

Viral contigs

Contiguous sequences assembled from overlapping sequence reads, which are then annotated as whole or partial viral genomes.

Multiple displacement amplification

A whole-genome amplification method, which starts by binding random primers to the template DNA and is then followed by strand displacement DNA synthesis performed by DNA polymerase, usually Φ29 DNA polymerase.

Primary immunodeficiencies

A group of rare immune disorders caused by genetic defects.

Meconium

The first stool of a neonate.

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Liang, G., Bushman, F.D. The human virome: assembly, composition and host interactions. Nat Rev Microbiol 19, 514–527 (2021). https://doi.org/10.1038/s41579-021-00536-5

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