Hidden potential of the virome

By | Science & Technology
Health human T cell. T cells play a vital role in the immune response. Production of CD4 and CD8 cells was shown to be affected by MRV exposure. Credit@ NIAID/NIH(NIAID Flickr'sphotostream) ViaWikimediCommons

The human body is a complex and sophisticated structure comprising of about 37.2 trillion cells according to a recent estimate. What connects all these cells is the simple fact that, be they erythrocytes or lymphocytes, heart cells or skin cells, they all contain an identical set of chromosomes. Each set of chromosomes providing a copy of the human genome, the instructions necessary to make a human.

Yet when compared to the host of microbes (bacteria, fungi and protozoa) that reside in the human body, human cells are outnumbered ten to one. These microbes provide valuable services and traits ranging from controlling obesity in the digestive system, to coping with mechanical challenges in the oral cavity. Yet what about the virome? Typically considered pathogenic, little work has been done to identify and quantify the viral load present (often inconspicuously) within the human body and light is only now being shed on the matter through deep sequencing. Such studies seem to show that a number of viruses are present in healthy individuals without challenging the immune system, or are held in check by the beneficial microbiota mentioned above.

One such example is Murine norovirus (MNV), a common enteric virus (i.e. found in the intestine) which may persist in mice with healthy immune systems non-intrusively, yet it causes an inflammatory pathology in mice without the At16L1 gene (a gene associated with Crohn’s syndrome in humans). Considering that similar phenomena may be observed with some bacteria of the body’s flora in immune defective test subjects despite them normally being beneficial, a recent study explored whether the occurrence of intestinal viruses may similarly be beneficial.

Many such studies use germ-free animals (GF), test subjects that have had their microbiotas removed, i.e. absence of microbes living in or on them, which live in controlled environments known as germ-free isolators. The absence of the microbiota in mice causes a number of abnormalities in the intestine and immune system, making them an interesting base model to study developmental effects of enteric viruses.

A Wistar rat, typically used in a laboratory setting before human trials commence. Credit@JanetStephens(photographer)ViaWikimediaCommons

A Wistar rat, typically used in a laboratory setting before human trials commence. Credit@JanetStephens(photographer)ViaWikimediaCommons

In this case, breeding pairs of GF mice were exposed to the MRV virus (strain CR6) and effects were studied on the pairs and their litter. MRV exposure restored to an extent the intestine and immune system of the test subjects. Specifically, in the intestine there was an increase in cellularity, i.e. type and number of cells, which in turn increased production of lysozyme and granules of Paneth cells, compounds used as antimicrobial agents and an integral part to the immune system. Additionally, there was an increase of CD4 T cells, which are an important part of the adaptive immune system and CD8 T cells, which are recruited to treat cancerous cells among other things.

Both initially exposed adults and offspring that inherited MRV from their parents, showed similar effects, removing the possibility of the effects being neonata. Additionally the beneficial effects only became evident in GF mice, with conventional mice carrying on unchanged after MRV exposure, suggesting that the viral benefits overlap with those provided by the bacterial flora. Supporting this idea, similar effects to MRV exposure were created to an extent, when bacteria (namely Bacteroides thetaiotaomicron and Lactobacillus johnsonii) were introduced to the mice.

The effects of MRV exposure was also tested in regards to different strains. In addition to CR6, CR3 and SKI strains were also used, producing the same effects albeit quantitatively distinct. Interestingly, the beneficial effects of MRV exposure, were absent in IFN-a receptor knockout mice (mice without the gene coding IFN-a receptor, an interferon receptor involved in the innate immune response against viral exposure), suggesting that the viral effects are dependent on the IFN-1 pathway.

The value of MRV in cases of microbiota depletion due to antibiotic use was also shown, as exposure restored intestine health, but furthermore provided chemical injury protection and alleviated the symptoms of Citrobacter rodentium by enhancing the immune response to bacterial virulence. So viral exposure might become routine treatment in countering the adverse effects of antibiotic cocktails. Regardless, there’s still much to learn about the “ecological” role of viruses within the human body.

What other benefits might the human body owe to viral presence?

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