Human virome

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The human virome is the total collection of viruses in and on the human body. [1] [2] [3] Viruses in the human body may infect both human cells and other microbes such as bacteria (as with bacteriophages). [4] Some viruses cause disease, while others may be asymptomatic. Certain viruses are also integrated into the human genome as proviruses or endogenous viral elements. [1]

Contents

Viruses evolve rapidly and hence the human virome changes constantly. [5] Every human being has a unique virome with a unique balance of species. [2] [6] Lifestyle, age, geographic location, and even the season of the year can affect an individual's exposure to viruses, and one's susceptibility to any disease that might be caused by those viruses is also affected by pre-existing immunity and both viral and human genetics. [7]

The human virome is far from being completely explored and new viruses are discovered frequently. Unlike the roughly 40 trillion bacteria in a typical human microbiome, [8] an estimate of the number of viral particles in a healthy adult human is not yet available, although virions generally outnumber individual bacteria 10:1 in nature. [9] Studying the virome is thought to provide an understanding of microbes in general and how they affect human health and disease.

In January 2024, biologists reported the discovery of "obelisks", a new class of viroid-like elements, and "oblins", their related group of proteins, in the human microbiome. [10] [11]

Methods and tools

Multiple methods are available for the isolation and study of human viruses:

Diversity of human viruses

The human virome in healthy, asymptomatic adults. The histogram shows the number of individuals (y-axis) who were positive for a given number of different viral genera (x-axis). Human virome 1.png
The human virome in healthy, asymptomatic adults. The histogram shows the number of individuals (y-axis) who were positive for a given number of different viral genera (x-axis).

The diversity of human viruses is vast and continually expanding. As of now, there are 219 known species of viruses that can infect humans. This number continues to grow with three to four new species being discovered every year.

The human virome is not stable and may change over time. In fact, new viruses are discovered constantly. [7] [17] [18] With an increasing number of known viruses, diagnosis and treatment of novel viral-associated conditions will become easier as well. [19] [20] Studying the virome could help improve drug development and limit antibiotic usage. [2] [18] [21]

One of the first studies that used high-throughput DNA sequencing to describe the diversity of eukaryotic dsDNA viruses in normal individuals included 706 samples from 102 subjects. [16] This study detected an average of 5.5 viral genera in each individual and these viruses included herpesviruses, papillomaviruses, polyomaviruses, adenoviruses, anelloviruses, parvoviruses, and circoviruses. [16]

The human virome in healthy, asymptomatic adults. The viral genera (y-axis) detected in each subject (x-axis) are represented by black bars. The virome of each individual is viewed by looking at the black bars in a given column. Human virome 2 1.png
The human virome in healthy, asymptomatic adults. The viral genera (y-axis) detected in each subject (x-axis) are represented by black bars. The virome of each individual is viewed by looking at the black bars in a given column.

Each individual had a distinct viral profile, demonstrating the high interpersonal diversity of the virome. One to 15 viral genera (average 5.5) were detected in 92% of the 102 individuals sampled (Figure 2). [16] Figure 3 illustrates the viromes of the 102 individuals defined by sampling up to five major body habitats, showing that a broad range of viruses was detected in healthy people (Figure 3). [16]

The 102 individuals carried seven distinct families of human DNA viruses (Figure 4A). [16] Sequences were detected predominantly in the nose and skin, similarity to 17 papillomavirus genera(Figure 4B). [16] Roseoloviruses, predominantly HHV-7 and to a lesser extent HHV-6, were present among 98% of the individuals who provided mouth samples. [16]

In addition, the same viruses were prevalent in multiple body habitats within individuals. For instance, the beta- and gamma-papillomaviruses were the viruses most commonly found in the skin and the nose (anterior nares; see Figure 4A,B), which may reflect proximity and similarities in microenvironments that support infection with these viruses. [16]

The human virome in five body habitats. (A) All of the viruses detected in the five body habitats . Each virus is represented by a colored bar and labeled on the y-axis on the right side. The relative height of the bar reflects the percentage of subjects sampled at each body site in whom the virus was detected. In this panel, the bar representing roseoloviruses in the oral samples reflects the maximum bar height, because 98% of the individuals who were sampled in the mouth harbored roseoloviruses. (B) This panel shows papillomaviruses included in the category 'Other papillomaviruses'. The largest bar height shown represents the unclassified papillomaviruses found in skin samples from 65% of subjects. Human virome.png
The human virome in five body habitats. (A) All of the viruses detected in the five body habitats . Each virus is represented by a colored bar and labeled on the y-axis on the right side. The relative height of the bar reflects the percentage of subjects sampled at each body site in whom the virus was detected. In this panel, the bar representing roseoloviruses in the oral samples reflects the maximum bar height, because 98% of the individuals who were sampled in the mouth harbored roseoloviruses. (B) This panel shows papillomaviruses included in the category ‘Other papillomaviruses’. The largest bar height shown represents the unclassified papillomaviruses found in skin samples from 65% of subjects.

The human blood virome

Whole-genome sequencing data of blood from 8,240 individuals without any clear infectious disease revealed 94 different viruses in 42% of the study participants. The sequences included 19 human DNA viruses, proviruses and RNA viruses (herpesviruses, anelloviruses, papillomaviruses, three polyomaviruses, adenovirus, HIV, HTLV, hepatitis B, hepatitis C, parvovirus B19, and influenza virus). [22] Of possible relevance to transfusion medicine, this study identified Merkel cell polyomavirus in 49 individuals, papillomavirus in blood of 13 individuals, parvovirus B19 in 6 individuals, and the presence of herpesvirus 8 in 3 individuals. [22]

Impact on human health

The human virome is a part of human bodies and will not always cause harm. [23] Many latent and asymptomatic viruses are present in the human body all the time. Viruses infect all life forms; therefore the bacterial, plant, and animal cells and material in the gut also carry viruses. [6] When viruses cause harm by infecting the cells in the body, a symptomatic disease may develop.

Contrary to common belief, harmful viruses may be in the minority, compared to benign viruses in the human body. It is much harder to identify viruses than it is to identify bacteria, therefore the understanding of benign viruses in the human body is very rudimentary. [2] The collection of all viruses in the human body which do not cause disease in healthy individuals is often referred to as the 'healthy human virome'. [23] The healthy virome consists of three distinct components: (i) viruses that systematically enter the human organism, primarily, with food, but do not replicate in humans; (ii) viruses infecting prokaryotes and, possibly, unicellular eukaryotes that comprise the healthy human microbiome; and (iii) viruses that actually replicate and persist in human cells. [23]

The health effects of viruses on an individual are dependent on the individual's immune system. [1] [20]

The hygiene hypothesis

Recent research has linked the emerging idea of the hygiene hypothesis to viruses. This hypothesis attempts to explain some of the high incidences of diseases such as asthma [24] and eczema [25] in the Western world by Western societies' overuse of antibiotic and antiviral agents.

This overuse potentially disrupts not only the bacteria of the gut but also the viruses that have long lived in harmony with the human body and now play a role in regulation of human health.

The hypothesis generally refers to microorganisms, but is now being extended to include airborne viruses and common viral infections of childhood that are becoming increasingly less common. [26]

Effect of skin location

Diverse viruses colonize the human skin and differ by skin site. [27] This skin virome includes human viruses (i.e. human papillomavirus) and bacteriophages (bacterial viruses) that infect commensal skin bacteria such as Staphylococci. [28]

Virus communities differ by moisture levels and degree of protection from the external environment. [27]

Effect of diet

Many studies have demonstrated that the bacteria and viruses in the human gut (the gut microbiome) can be altered by changes in diet. [29] One study that focused on bacterial viruses, called bacteriophages, in the gut found a significant relationship between diet and the type of bacteriophages present. [30] This was done by comparing the distance between bacteriophage gut communities in individuals both before and after they started a controlled diet. The results were that the distance between the bacteriophage gut communities of individuals on the same diet was significantly smaller at the end of their dietary treatment than it was at the start, while there was no increase in community similarity for individuals on different diets over time.

Related Research Articles

<span class="mw-page-title-main">Bacteriophage</span> Virus that infects and replicates within bacteria

A bacteriophage, also known informally as a phage, is a virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν, meaning "to devour". Bacteriophages are composed of proteins that encapsulate a DNA or RNA genome, and may have structures that are either simple or elaborate. Their genomes may encode as few as four genes and as many as hundreds of genes. Phages replicate within the bacterium following the injection of their genome into its cytoplasm.

<span class="mw-page-title-main">DNA virus</span> Virus that has DNA as its genetic material

A DNA virus is a virus that has a genome made of deoxyribonucleic acid (DNA) that is replicated by a DNA polymerase. They can be divided between those that have two strands of DNA in their genome, called double-stranded DNA (dsDNA) viruses, and those that have one strand of DNA in their genome, called single-stranded DNA (ssDNA) viruses. dsDNA viruses primarily belong to two realms: Duplodnaviria and Varidnaviria, and ssDNA viruses are almost exclusively assigned to the realm Monodnaviria, which also includes some dsDNA viruses. Additionally, many DNA viruses are unassigned to higher taxa. Reverse transcribing viruses, which have a DNA genome that is replicated through an RNA intermediate by a reverse transcriptase, are classified into the kingdom Pararnavirae in the realm Riboviria.

<span class="mw-page-title-main">Virology</span> Study of viruses

Virology is the scientific study of biological viruses. It is a subfield of microbiology that focuses on their detection, structure, classification and evolution, their methods of infection and exploitation of host cells for reproduction, their interaction with host organism physiology and immunity, the diseases they cause, the techniques to isolate and culture them, and their use in research and therapy.

<span class="mw-page-title-main">Human microbiome</span> Microorganisms in or on human skin and biofluids

The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the gastrointestinal tract, skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, and the biliary tract. Types of human microbiota include bacteria, archaea, fungi, protists, and viruses. Though micro-animals can also live on the human body, they are typically excluded from this definition. In the context of genomics, the term human microbiome is sometimes used to refer to the collective genomes of resident microorganisms; however, the term human metagenome has the same meaning.

<span class="mw-page-title-main">Prophage</span> Bacteriophage genome that is integrated into a bacterial cell

A prophage is a bacteriophage genome that is integrated into the circular bacterial chromosome or exists as an extrachromosomal plasmid within the bacterial cell. Integration of prophages into the bacterial host is the characteristic step of the lysogenic cycle of temperate phages. Prophages remain latent in the genome through multiple cell divisions until activation by an external factor, such as UV light, leading to production of new phage particles that will lyse the cell and spread. As ubiquitous mobile genetic elements, prophages play important roles in bacterial genetics and evolution, such as in the acquisition of virulence factors.

<span class="mw-page-title-main">Lysogenic cycle</span> Process of virus reproduction

Lysogeny, or the lysogenic cycle, is one of two cycles of viral reproduction. Lysogeny is characterized by integration of the bacteriophage nucleic acid into the host bacterium's genome or formation of a circular replicon in the bacterial cytoplasm. In this condition the bacterium continues to live and reproduce normally, while the bacteriophage lies in a dormant state in the host cell. The genetic material of the bacteriophage, called a prophage, can be transmitted to daughter cells at each subsequent cell division, and later events can release it, causing proliferation of new phages via the lytic cycle.

<span class="mw-page-title-main">Introduction to viruses</span> Non-technical introduction to viruses

A virus is a tiny infectious agent that reproduces inside the cells of living hosts. When infected, the host cell is forced to rapidly produce thousands of identical copies of the original virus. Unlike most living things, viruses do not have cells that divide; new viruses assemble in the infected host cell. But unlike simpler infectious agents like prions, they contain genes, which allow them to mutate and evolve. Over 4,800 species of viruses have been described in detail out of the millions in the environment. Their origin is unclear: some may have evolved from plasmids—pieces of DNA that can move between cells—while others may have evolved from bacteria.

<span class="mw-page-title-main">Human Microbiome Project</span> Former research initiative

The Human Microbiome Project (HMP) was a United States National Institutes of Health (NIH) research initiative to improve understanding of the microbiota involved in human health and disease. Launched in 2007, the first phase (HMP1) focused on identifying and characterizing human microbiota. The second phase, known as the Integrative Human Microbiome Project (iHMP) launched in 2014 with the aim of generating resources to characterize the microbiome and elucidating the roles of microbes in health and disease states. The program received $170 million in funding by the NIH Common Fund from 2007 to 2016.

Merkel cell polyomavirus was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called digital transcriptome subtraction. MCV is one of seven currently known human oncoviruses. It is suspected to cause the majority of cases of Merkel cell carcinoma, a rare but aggressive form of skin cancer. Approximately 80% of Merkel cell carcinoma (MCC) tumors have been found to be infected with MCV. MCV appears to be a common—if not universal—infection of older children and adults. It is found in respiratory secretions, suggesting that it might be transmitted via a respiratory route. However, it has also been found elsewhere, such as in shedded healthy skin and gastrointestinal tract tissues, thus its precise mode of transmission remains unknown. In addition, recent studies suggest that this virus may latently infect the human sera and peripheral blood mononuclear cells.

<span class="mw-page-title-main">Virus</span> Infectious agent that replicates in cells

A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are found in almost every ecosystem on Earth and are the most numerous type of biological entity. Since Dmitri Ivanovsky's 1892 article describing a non-bacterial pathogen infecting tobacco plants and the discovery of the tobacco mosaic virus by Martinus Beijerinck in 1898, more than 11,000 of the millions of virus species have been described in detail. The study of viruses is known as virology, a subspeciality of microbiology.

<span class="mw-page-title-main">Microbiota</span> Community of microorganisms

Microbiota are the range of microorganisms that may be commensal, mutualistic, or pathogenic found in and on all multicellular organisms, including plants. Microbiota include bacteria, archaea, protists, fungi, and viruses, and have been found to be crucial for immunologic, hormonal, and metabolic homeostasis of their host.

The lung microbiota is the pulmonary microbial community consisting of a complex variety of microorganisms found in the lower respiratory tract particularly on the mucous layer and the epithelial surfaces. These microorganisms include bacteria, fungi, viruses and bacteriophages. The bacterial part of the microbiota has been more closely studied. It consists of a core of nine genera: Prevotella, Sphingomonas, Pseudomonas, Acinetobacter, Fusobacterium, Megasphaera, Veillonella, Staphylococcus, and Streptococcus. They are aerobes as well as anaerobes and aerotolerant bacteria. The microbial communities are highly variable in particular individuals and compose of about 140 distinct families. The bronchial tree for instance contains a mean of 2000 bacterial genomes per cm2 surface. The harmful or potentially harmful bacteria are also detected routinely in respiratory specimens. The most significant are Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae. They are known to cause respiratory disorders under particular conditions namely if the human immune system is impaired. The mechanism by which they persist in the lower airways in healthy individuals is unknown.

In biology, a pathogen, in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ.

Biological dark matter is an informal term for unclassified or poorly understood genetic material. This genetic material may refer to genetic material produced by unclassified microorganisms. By extension, biological dark matter may also refer to the un-isolated microorganism whose existence can only be inferred from the genetic material that they produce. Some of the genetic material may not fall under the three existing domains of life: Bacteria, Archaea and Eukaryota; thus, it has been suggested that a possible fourth domain of life may yet be discovered, although other explanations are also probable. Alternatively, the genetic material may refer to non-coding DNA and non-coding RNA produced by known organisms.

<span class="mw-page-title-main">Viral metagenomics</span>

Viral metagenomics uses metagenomic technologies to detect viral genomic material from diverse environmental and clinical samples. Viruses are the most abundant biological entity and are extremely diverse; however, only a small fraction of viruses have been sequenced and only an even smaller fraction have been isolated and cultured. Sequencing viruses can be challenging because viruses lack a universally conserved marker gene so gene-based approaches are limited. Metagenomics can be used to study and analyze unculturable viruses and has been an important tool in understanding viral diversity and abundance and in the discovery of novel viruses. For example, metagenomics methods have been used to describe viruses associated with cancerous tumors and in terrestrial ecosystems.

<span class="mw-page-title-main">CrAssphage</span>

CrAss-like phage are a bacteriophage family that was discovered in 2014 by cross assembling reads in human fecal metagenomes. In silico comparative genomics and taxonomic analysis have found that crAss-like phages represent a highly abundant and diverse family of viruses. CrAss-like phage were predicted to infect bacteria of the Bacteroidota phylum and the prediction was later confirmed when the first crAss-like phage (crAss001) was isolated on a Bacteroidota host in 2018. The presence of crAss-like phage in the human gut microbiota is not yet associated with any health condition.

<span class="mw-page-title-main">Virome</span>

Virome refers to the assemblage of viruses that is often investigated and described by metagenomic sequencing of viral nucleic acids that are found associated with a particular ecosystem, organism or holobiont. The word is frequently used to describe environmental viral shotgun metagenomes. Viruses, including bacteriophages, are found in all environments, and studies of the virome have provided insights into nutrient cycling, development of immunity, and a major source of genes through lysogenic conversion. Also, the human virome has been characterized in nine organs of 31 Finnish individuals using qPCR and NGS methodologies.

<span class="mw-page-title-main">Marine viruses</span> Viruses found in marine environments

Marine viruses are defined by their habitat as viruses that are found in marine environments, that is, in the saltwater of seas or oceans or the brackish water of coastal estuaries. Viruses are small infectious agents that can only replicate inside the living cells of a host organism, because they need the replication machinery of the host to do so. They can infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea.

<i>Duplodnaviria</i> Realm of viruses

Duplodnaviria is a realm of viruses that includes all double-stranded DNA viruses that encode the HK97 fold major capsid protein. The HK97 fold major capsid protein is the primary component of the viral capsid, which stores the viral deoxyribonucleic acid (DNA). Viruses in the realm also share a number of other characteristics, such as an icosahedral capsid, an opening in the viral capsid called a portal, a protease enzyme that empties the inside of the capsid prior to DNA packaging, and a terminase enzyme that packages viral DNA into the capsid.

<span class="mw-page-title-main">Phageome</span> Collection of bacteriophages found in a particular environment

A phageome is a community of bacteriophages and their metagenomes localized in a particular environment, similar to a microbiome. The term was first used in an article by Modi et al in 2013 and has continued to be used in scientific articles that relate to bacteriophages and their metagenomes. A bacteriophage, or phage for short, is a virus that has the ability to infect bacteria and archaea, and can replicate inside of them. Phageome is a subcategory of virome, which is all of the viruses that are associated with a host or environment. Phages make up the majority of most viromes and are currently understood as being the most abundant organism. Oftentimes scientists will look only at a phageome instead of a virome while conducting research.

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Further reading