The COVID-19 pandemic has highlighted the devastating effect a virus can have on the world’s population.  Other familiar viruses that affect people are the influenza virus, the Ebola virus, and the human immunodeficiency virus (HIV). 

The human body is no stranger to viruses and there is indeed a viper’s nest of viruses in and on the body!  Not only viruses, but there are also other microorganisms such as bacteria, fungi, and archaea (primitive single-celled organisms) present and in such large numbers that they are viewed as one of the organs of the body.   The bacteria and these other microbes make up what is known as the microbiome, which means “small living community”. 

The viruses in the human body are collectively known as the human virome and are present in large numbers, estimated to be closely comparable to the total number of cells in the human body.

Viruses are tiny particles that exist in unaccountable numbers and are so small that they can’t be seen with a normal microscope.  To give an indication of scale, should a virus be enlarged to the size of the full stop at the end of this sentence, then humans would be almost 6 km tall.

Types of viruses:

Viruses differ from bacteria, as they are not made of cells like bacteria, but consist of a piece of DNA that is packed within a protein shell, also known as a coat.  There are two broad categories of viruses in the human virome:

  • Viruses that infect and live on the bacteria in and on our bodies, called bacteriophage viruses, also simply known as phages.
  • Viruses that infect cells of the human host, called eukaryotic viruses.  Some of these viruses can cause acute infection, while other viruses can be latent and asymptomatic.  Some viruses appear to colonize human cells benignly, often over long periods of time.

Most constituents of the virome are suspected to be phages.  Interestingly, phages reproduce by attaching to a bacterial cell and then injecting its DNA into the bacterial cell.  The bacterial cell then turns into a phage factory to produce as many as 100 new phages before it bursts and releases the phages, which then attack more bacteria.   Consequently, phages can grow quicker than bacteria.  In recent experimental studies, phages were used to treat bacterial infections.  Once the type of bacteria is known, the patient is given a phage that is known to infect and kill that type of bacteria.   However promising this type of treatment may seem to be, much further research is needed in this regard.

To prevent themselves from being wiped out, bacteria have defense systems against phages, such as preventing the phage from attaching, chopping up the phage’s DNA upon entering the bacterial cell, or even committing cell “suicide” to prevent the phage from multiplying.  In addition, the very crowded microbe environment in the gut can result in the phage not finding its correct bacterial target.

Characteristics of the human virome:

  • The human virome is vast and composed of an estimated 1013 particles in any individual person.
  • Some viruses can cause disease, while others may be asymptomatic, or integrate into the human genome.
  • Viruses evolve rapidly, which means the human virome changes constantly.
  • Every person has a unique virome, with a unique balance of species.
  • The virome in a healthy adult is usually relatively stable over time.
  • Destabilization of the virome is often associated with disease states.
  • New viruses are discovered frequently and the human virome is far from being completely explored.
  • Human virome contains a large proportion of viral “dark matter”, which refers to the majority of viral sequences that are unfamiliar and do not look like anything else in available databases.   (The National Center for Biotechnology Information in the USA had by February 2021 listed about 10 500 complete human viral genome sequences, which is a tiny fraction of the estimated global diversity.)
  • Viruses that colonize the human body interact with one another and can trigger the human immune cells and activate immune responses.

Sites of the human virome:

Viral populations vary greatly across the human body, with a diverse composition of viruses, primarily due to the wide variety of host bacteria in different anatomical sites.

  • The gastrointestinal tract (gut) contains the most abundant populations of microorganisms, such as bacteria and viruses.  As the gut is rich in human cells and bacteria, it provides a rich variety of hosts for viral growth, with phages the most abundant viral population.
  • The oral cavity contains a vast abundance of complex microbial populations and diverse viral communities.  Additional microenvironments in the oral cavity, such as plaque, also show abundant viral populations.
  • The respiratory tract has shown in virome analysis that a healthy lung and respiratory tract can be populated by large viral communities.
  • Blood contains both eukaryotic and phage viruses and has been widely studied, also with the aim of assessing the safety of donor blood supplies, yet much remains to be learnt about the blood virome of healthy individuals.  A study published in January 2023 has identified 56 different viruses from 37 viral families in the blood of 1200 healthy individuals.
  • The skin has a relatively low microbial biomass.  The human skin is colonized by diverse viruses, which differ by skin site due to variations in moisture levels as well as the degree of protection from the external environment. 
  • The urogenital system contains mixtures of viruses, botheukaryotic viruses that replicate in human cells and phage viruses from the resident bacteria.
  • The nervous system has not been widely studied to determine virome populations in healthy people, but cerebral fluid has been found to have detectable viral colonization, showing low levels of viruses, including phages.

Factors that shape the human virome:

Apart from anatomical location, recent studies have uncovered various factors that show associations with virome structure, and which may affect health. 

  • Diet can affect the human virome, starting with the newborn infant and depending on whether breast milk or formula feeding was used.  Breastfeeding is well known to have a protective effect due to its antiviral components, which inhibit viruses.   Diet also affects the virome in adults.  Studies have indicated that individuals on the same diet have more similar viral compositions than individuals on different diets.
  • Genetics of the individual has long been studied to find how human genetics can influence the virome.  Recent studies have reported that genetics have little effect, and that the environment plays a more important role.
  • Geography seems to have the strongest impact on the virome, compared to other factors.  Studies have shown that geographic location and a random distribution of colonization have strong impacts on human virome variation.  A recent study found a higher viral diversity in populations from non-western countries, indicating the prominent effects of geography.
  • Age plays a role in viral diversities, as viral diversities in early life and in individuals older than 65 are lower than in healthy adults between 18 and 65 years of age.
  • Cohabitation is also a factor playing a role, as members of the same household share more similarity in the oral virome than individuals from different households.
  • Medication also has an effect on the human virome, as indicated in a Chinese study.
  • Disease interacts with the virome and studies in this regard are just starting.  Many individual viruses are known to cause disease and even mortality and studies have begun to show viral population patterns associated with disease states.

Conclusion:

Interest in the human virome has increase over the past number of years and the pace of virus identification has increased, due to advances in virus identifying technology and the updating of viral genome databases.

New viruses are discovered frequently and the human virome is far from being completely explored.  Further studies would assist in providing a better understanding of the virome in general and how it affects human health and disease.

References:

The human virome: Assembly, composition, and host interactions.  Published 30 March 2021 in the journal Nature Reviews Microbiology.  Nature.  (www.nature.com)

What is the human virome.  Information updated 30 March 2022.  News Medical.  (www.news-medical.net)

The human virome: Viral metagenomics, relations with human diseases, and therapeutic applications.  Published February 2022 in the journal Viruses.  PubMed Central.  National Centre for Biotechnology Information.  US National Library for Medicine. National Institutes of Health.  USA.  (www.ncbi.nlm.nih.gov)

Illuminating the human virome in health and disease.  Published 30 July 2022 in the journal Genome Medicine.  BioMed Central.  (www.genomemedicine.biomedcentral.com)

The gut virome: A new microbiome component in health and disease.  Published July 2022 in the journal eBiomedicine.  PubMed Central.  National Centre for Biotechnology Information.  US National Library for Medicine. National Institutes of Health.  USA.  (www.ncbi.nlm.nih.gov)

Human virome.  Updated 7 October 2023.  Wikipedia.  The Free Encyclopedia.  (www.wikipedia.org)

Bacteriophages: Viruses that infect bacteria.  Published 2 July 2019.  Frontiers for Young Minds.  Frontiers.  (www.kids.frontiersin.org)

 An atlas of the blood virome in healthy individuals.  Published 2 January 2023 in the journal Virus Research, Volume 323.  ScienceDirect.  (www.sciencedirect.com)

HEALTH INSIGHT.

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