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Review
. 2021 Aug;19(8):514-527.
doi: 10.1038/s41579-021-00536-5. Epub 2021 Mar 30.

The human virome: assembly, composition and host interactions

Guanxiang Liang  1 , Frederic D Bushman  2
Affiliations
Review

The human virome: assembly, composition and host interactions

Guanxiang Liang et al. Nat Rev Microbiol. 2021 Aug.

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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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Phage replication cycles.
Phages can engage in four types of interactions with their hosts. In lytic growth, phages infect cells, produce viral macromolecules, assemble new particles and lyse host cells, thereby liberating new viral particles. In lysogenic growth, phages inject their genomes into cells, and the genomes then become integrated into the bacterial cellular chromosome. The prophage is maintained in a quiescent state until detection of a suitable induction signal, after which the phage genome becomes excised and goes on to direct lytic growth. Pseudolysogeny is a loose interaction between the phage and the host in which the phage genome is present in the bacterial cell but not actively directing lytic growth. Lastly, some phages such as the filamentous phages (Inoviridae) can infect cells and preserve the infected cell while producing new phage progeny by budding.
Fig. 2
Fig. 2. The human virome at different body sites.
Summary of viruses found at each human body site. Viral types are summarized from published virome surveys,,,,–,–,–,–; those known at each body site are likely to increase as more human populations are surveyed and more viral types are discovered. In a few cases, viral lineages were excluded from the analysis because they likely represent contaminants or misattributions. These exclusions include mimivirus, phycodnavirus, marseillevirus, flaviviruses and poxviruses in blood, and baculovirus in the vagina. VLP, virus-like particle.
Fig. 3
Fig. 3. Stepwise assembly of the paediatric virome.
Healthy neonates are typically born lacking a gut virome or microbiome. Pioneering bacteria colonize the gut of the neonate, such that infants have a detectable microbiome by month 1 of life. These bacteria commonly harbour integrated prophages, which occasionally induce prophages, providing a first wave of viral particles in the gut. Later, by month 4, more viruses that infect human cells can be detected. Infection with these viruses, some of which can be pathogenic, is inhibited by breastfeeding. Breastfeeding can also alter the types of phages present by altering the proportions of bacteria in the infant gut, which consequently alters the proportions of their phages. The protective effects of breast milk can be conferred by maternal immune cells or various macromolecules. These include maternal antibodies, human milk oligosaccharides, lactoferrin, mucin and gangliosides. The viral groups targeted by each antiviral factor in human breast milk are shown. Supporting references include refs,,–,. HSV, herpes simplex viruses; RSV, respiratory syncytial virus; SARS-CoV; severe acute respiratory syndrome coronavirus; VZV, varicella zoster virus.
Fig. 4
Fig. 4. Factors that shape the human virome.
Major factors include the diet, breast milk or formula feeding,, medications (including antibiotics and immunosuppressants),, host genetics,,,,,, cohabitation, geography,,–, presence of disease (Table 1) and ageing.
Fig. 5
Fig. 5. Host–virome interactions.
Eukaryotic viruses have both detrimental (red arrow) and beneficial (blue arrow) effects on host health. Phages interact with the host directly or indirectly via the host-associated bacterial community and pose undetermined effects (green arrow) on host health. Data based on refs,–,–. TLR, Toll-like receptor.
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