New test developed that rapidly profiles the human virome

Molecular representation of an antibody (green) binding with an HIV virus (red and yellow).

The viruses that live in our body may be just as important to our health and development as their bacterial counterparts.  Unfortunately, testing which ones currently exist, or have at point infected us is expensive, time consuming, and laborious using current techniques.  Making matters worse, these techniques, which usually rely on measuring the amount of antibodies against specific viruses that exist in our blood, are often times ineffective when the antibodies are in low levels.  Recently though, scientists from Harvard University developed a new technique that can accurately, rapidly, and inexpensively (~$25) screen for the existence of over 200 viral antibodies in less than a drop of blood.  They call their technique VirScan, and they published their method last week in Science.

The scientists combined two advanced biological screening tools to create their method: DNA microarray synthesis and phage display.  In short, the scientists created libraries of peptides that represented 206 known human viruses, like HIV and influenza, and expressed them on simple bacteriophages.  They then combined these bacteriophages with a drop of blood, which itself contains antibodies that combat viruses that someone currently has, or has been infected from in the past.  The antibodies that exist specifically bind to the phages that represent a virus.  They then eliminate all the phages not bound to antibodies, and measuring what remains gives the scientist an indication of which antibodies were in the blood.  This explanation of the researchers’ technique may not satisfy our more curious readers, so those that wish to learn more should definitely check out the paper. When the scientists screened over 500 people using this method, the results showed that most people tested positive on average for 10 viruses (i.e. they had antibodies against these viruses).  Interestingly, 2 individuals tested positive for 84/206 viruses.  The most commonly detected virus was Epstein-Barr virus, followed by types of rhinovirus (common cold), and adenovirus.  Also of interest was that the viral structures differed geographically between continents.

This assay has many immediate implications in many areas.  The most obvious is its use as a diagnostic tool for easily screening people for their viruses.  In addition though, by discovering which peptides antibodies efficiently bind to, and how those differ between humans, more effective vaccines can be developed that treat more people.  Also, it should be interesting to discover how infection with certain viruses influences long term health and chronic disease.  For example, were those two individuals that tested positive for antibodies against 84 viruses more, or less healthy than those who tested positive for very few, and whether infection with certain viruses is associated with any chronic conditions.

Schizophrenia and the virome

Schizophrenia PET scan

Schizophrenia is a mental health disorder in which people cannot recognize reality, suffer from hallucinations, and experience social withdrawal.  The causes of schizophrenia are unknown, but it is thought to include genetic, environmental, psychological, and social risk factors.  As we have written about extensively in this blog, the bacteria and viruses in our body have an important connection to our brain and behavior, in what has been termed the ‘gut-brain axis’.  Considering the gut-brain axis, a team of scientists from Johns Hopkins University wondered if the microbiome, and specifically the virome, was somehow related schizophrenia.  They recently published their findings in Schizophrenia Bulletin.

The scientists sampled the throat microbiome from 74 people in the Baltimore, MD area, 41 of whom suffered from schizophrenia and 33 of whom did not.  They discovered that a specific bacteriophage (virus that infects bacteria), Lactobacillus phage phaidh, was linked to schizophrenia, which was found in 17 of the 41 schizophrenia patients, but only 1 of the 33 control individuals.  In addition, 9 of those 17 schizophrenics had a comorbid immune disorder, such as diabetes or Crohn’s disease, whereas only 2 of the remaining schizophrenics without the phage had these diseases.  The scientists also found a loose link between taking the drug valproate and occurrence of the phage.  Interestingly, this drug has been previously shown to affect the microbiome.  Finally, the existence of the phage coincided with higher levels of the bacteria that the phage attacks, Lactobacillus gasseri.  This is an unsurprising result because a phage and its target are usually found together.

The scientists acknowledge that the results of this study do not prove any real association between the microbiome and schizophrenia, but based on the results, they suggest that further research is warranted.  Notably, Lactobacillus gasseri is sometimes included in probiotics to supposedly relieve gastrointestinal issues.  However, if gasseri’s phaidh phage goes along with it, then according to this study, it may cause more harm than good.

Viruses in the gut connected to inflammatory bowel disease

Drawing of a bacteriophage

A new study has shown that the composition of viruses in the gut may play an important role in inflammatory bowel diseases (IBD).  If you’ve been reading the blog for a while, you’ve seen us write about something called the virome. The virome is the collection of viruses in the body and similarly to the microbiome, it may have profound affects on human health. This study led by scientists at Washington University in St. Louis and published in Cell is the first to correlate a disease with changes in a person’s virome.

IBD, specifically Crohn’s disease and ulcerative colitis (UC), are diseases that have been characterized by decreased bacterial diversity in the gut.  However in this study, the scientists found that patients with Crohn’s and UC showed greater diversity of viruses than healthy individuals.  This suggested that viruses played a role in the disease.

The team of scientists studied individuals in Boston, Chicago, and the United Kingdom with the disease. They took stool samples from patients with UC and Crohn’s and sequenced their viral DNA. They compared this to the viruses in stool samples from healthy individuals living in the same areas and households. Patients with the disease had a higher number of viruses than those without IBD. Specifically, they found that Crohn’s and UC patients had higher levels of Caudovirales bacteriophages (viruses that infect bacteria) that were specific to each disease.

Further research is needed to better understand the relationship between the virome and the microbiome but as we see from the increase in bacteriophages, there is certainly a relationship between these two systems. While the authors state that it does not look as if changes in the virome were secondary to changes in bacterial populations, it is not yet clear if changes in the virome are the result of bacterial alterations in the gut or if it may lead to microbiome changes - or a combination of the two.  This study is the first of its kind to show a connection between disease and the virome and I think we are going to see several more studies in the coming years showing this type of correlation with disease.  While we generally think of viruses as causing infections like influenza, their impact on chronic disease may be vast.  

Our beneficial relationship with our virome

X-ray crystallographic structure of a Norovirus capsid.

We have been championing the virome since the inception of the AMI.  We believe that with time, viruses will prove equally as important as bacteria within the microbiome.  To this end, a paper published last week in Nature shows evidence that a specific virus can promote a healthy gut in mice the same way that bacteria do.  The virus, murine norovirus (MNV), was able to successfully restore function to mice with compromised guts.

The authors started with two groups of mice, a control group and a germ-free group.  The control group had normal guts and immune function as measured by gut morphology, and the amount of T-cells.  The germ free mice had thin, leaky guts, and low levels of T-cells.  The scientists infected these germ free mice with MNV and allowed it to proliferate.  Upon investigation of these mice, their gut integrity and immune function resembled the control group.  A second experiment was performed on mice that had been given a course of antibiotics that wiped out the normal microbiome and resulted in an abnormal immune system and compromised gut.  When these mice were infected with MNV they too saw an improvement in health.  In a final experiment mice were given pathogenic bacteria that damaged the gut, but when infected with the virus the negative effects from the pathogens were diminished.

Viruses have a bad reputation, but that’s because we generally only care about the ones that make us sick.  There are countless viruses that exist in our guts though, many that we do not interact with at all, and many symbiotic ones which have yet to be discovered.  It is time that we appreciate the entirety of our microbiome, not just the bacteria but the eukaryotes, archaea, fungi, and viruses as well.

Is our virome lowering our intelligence?

We have talked about the virome and its possible substantial impact on human health on this blog before.  Lately, the virome has been getting a lot of press about its potential beneficial aspects, but today we want to discuss a negative one.  A paper was recently published in the Proceedings of the National Academy of Sciences that identified a specific virus in the virome that may be directly affecting the brain, and lowering our aptitude for spatial awareness and attention. 

Researchers were testing the oral microbiome of a cohort of people who were also taking intelligence tests as part of a separate, unrelated, study.  After genome sequencing they noticed the conspicuous existence of a virus, known as Chlorovirus ATCV-1, in about half the study population.  This virus was known to exist in algae, but had never been identified in humans, and there it was, affecting half there population.  Moreover, the virus cut across all demographics in there study, and was not related to age, race, or gender.  When the scientists compared the intelligence tests of those who had the virus versus those that did not, those that had the virus scored slightly less on tests involving spatial awareness.  However, they are quick to note that other tests for intelligence were unaffected.  They reiterate that these scores were related to the existence of the virus and not any specific demographic.

The scientists tried to recreate these results in mice.  They infected a group of mice with the virus and compared its scores on spatial tests with a control group.  The group that had the virus scored considerably lower on the tests.  When they measured specific genes that were affected in the infected mice they discovered some that related to dopamine regulation, which is known to be critical to memory formation and learning. 

Overall this fascinating study not only identified a new member of our virome, but showed that this virus may be altering our spatial reasoning abilities.  So the next time your significant other yells at you for getting lost, just blame it on your virome!

The virome

Bacteriophages (bacterial viruses) attached to a bacterial cell wall.

A review in the journal Cell written by Herbert Virgin describes the exploration of the virome, a part of the overall microbiome which includes viruses, as an emerging study of importance in relation to human health. The size of the mammalian virome –viruses that infect mammals- is still unknown, but it is believed by scientists that, in the human body, viruses may outnumber the bacterial microbiome by at least 10x, making the virome out number human cells by 100 times or more. 

The human virome includes all the viruses that affect human cells, along with those that affect our bacterial, archaeal, and fungal microbiome, in addition to other viral derived genetic material.  Viruses have already been studied as important pathogens for each of these hosts, but their mutualistic and beneficial interactions are only beginning to be explored.  This is similar to the story of bacteria, which are only now being recognized for their importance in humans.  In addition, it appears there are many important, complex interactions within the microbiome that include the virome.  For example, it is likely that viruses that attack bacteria are embedded in the gut mucous and attack and destroy bacteria before the bacteria can reach the gut lining, providing host immunity.

Investigation into the viral microbiome is still at its beginning. Discovery of new viruses and their interactions with humans is likely to continue and perhaps increase with the increase in availability of viral genome information.  We encourage everyone to read the linked article.  The virome is a fascinating subject which we hope to explore in future blog posts.