The human virome represents the complete collection of viruses existing within and on the human body. This includes viruses that can infect human cells and those that infect other microorganisms, such as bacteria. While the human microbiome, comprising bacteria, fungi, and other microbes, is widely recognized, the virome forms a distinct yet interconnected component of this complex internal ecosystem. Unlike the bacterial microbiome, which is often stable in adults, the virome is constantly changing, reflecting a dynamic balance of viral populations.
Composition of the Human Virome
The human virome consists of a diverse range of viral types, each playing a different role within the body. Bacteriophages, or phages, are the most abundant viruses in the human body and specifically infect bacteria, not human cells. These phages can be found in high numbers, particularly in the gut, where they influence bacterial populations. Examples of phage families commonly found include Caudovirales and Microviridae.
Alongside phages are eukaryotic viruses, which directly infect human cells. These can cause acute infections, like influenza, or establish latent or persistent infections without immediate symptoms. Herpesviruses, adenoviruses, and anelloviruses are examples of eukaryotic DNA viruses frequently detected in various body sites, including the gut, oral cavity, and respiratory tract.
A unique component of the human virome involves endogenous retroviruses (ERVs), which are ancient viral DNA sequences integrated directly into the human genome. These viral remnants are passed down through generations and make up a significant portion of our DNA, around 8%. While most ERVs no longer produce infectious viral particles, some have acquired new functions over evolutionary time, such as the syncytin genes, which are derived from retroviruses and are involved in the formation of the human placenta.
Acquiring and Shaping Your Virome
The collection of viruses within an individual begins to assemble early in life, influenced by various exposures. At birth, infants acquire some viruses from their mother, though initial viral colonization in the neonatal gut is primarily driven by environmental factors.
Environmental exposure significantly contributes to the shaping of the virome throughout life. Contact with other individuals, animals, and the broader environment introduces new viral communities. Factors like the presence of older siblings and residential location can impact the gut virome in infants.
Diet also serves as a major source of new viruses, particularly through the consumption of food and water. Dietary factors influence the gut virome, with the timing of introducing certain foods potentially affecting viral diversity.
The Virome’s Role in Human Health
The virome plays a multifaceted role in human health, extending beyond the traditional understanding of viruses as solely disease-causing agents. Bacteriophages can exert beneficial effects by modulating bacterial populations. Phages help maintain the balance of the gut microbiome by targeting and eliminating specific bacteria, preventing any single bacterial species from becoming overly dominant. This contributes to microbial diversity and stability, which supports host functions like immune defense and metabolic processes.
Certain viral infections can also contribute to immune system development and modulation. Persistent viral infections can stimulate innate immunity and provide protection against other infectious agents. For example, chronic herpesvirus infection can benefit its host by stimulating innate immune responses. The interactions between viruses, bacteria, and host immunity are complex, with outcomes dependent on factors like anatomical location, host genetics, and the presence of other microbes.
Despite these beneficial interactions, the virome also includes viruses with pathogenic potential. These can cause acute infections, such as the common cold, or establish chronic and latent infections that may impact long-term health. The interplay between these pathogenic viruses and the host’s immune system, often influenced by the broader microbiome, can determine the severity and outcome of disease. Viral DNA and RNA can trigger immune responses, leading to inflammation.
Connection to Specific Diseases
Imbalances within the human virome, often referred to as dysbiosis, have been linked to various specific health conditions. Inflammatory Bowel Disease (IBD) is one such condition where the enteric virome has been observed to be abnormal. An increased abundance of certain bacteriophage families has been observed in individuals with IBD, suggesting a potential role for these phages in disease progression.
Type 1 Diabetes (T1D), an autoimmune disorder, also shows associations with changes in the intestinal virome. Children at risk for T1D or those who develop autoimmunity tend to have less diverse intestinal viromes compared to healthy controls. Specific components of the virome have been linked to the development of autoimmunity in these individuals, with changes in the virome often preceding the onset of autoantibodies.
Beyond these conditions, the virome’s influence extends to other autoimmune disorders and neurodegenerative diseases. Viral infections are considered potential triggers for the immune system to mistakenly attack the body’s own tissues, which can lead to autoimmune conditions and certain neurodegenerative disorders. Various viruses found at higher frequencies in affected tissues suggest a broader viral involvement in autoimmune disease development.
Studying the Human Virome
Scientists primarily study the human virome using metagenomic sequencing, which involves analyzing all the genetic material in a sample. This approach allows for the identification of known viruses and the discovery of novel ones without requiring them to be grown in laboratory cultures. Samples from various body sites are collected, and their viral nucleic acids are extracted, amplified, and sequenced.
Despite advancements in sequencing technologies, a substantial portion of the detected viral sequences remains uncharacterized. This unannotated genetic material is often referred to as “viral dark matter.” Only a small percentage of viruses found in the human gut show similarity to known viruses in existing databases. Identifying and understanding this viral dark matter is an ongoing challenge, as it represents a vast reservoir of viral diversity with unknown functions and host interactions.