The Largest—and Most Overlooked—Part of the Microbiome? Viruses

by Marie Veronique

 

At Marie Veronique, we focus on learning everything we can about the roles the various microbiomes in our body play in keeping us, and in particular our skin, healthy. We’ve become so familiar with microbes like Propionibacterium acnes and Staphylococcus epidermidis that they practically feel like our next door neighbors.

In actuality, these bacteria and millions of others like them are even closer to us than our real next door neighbors because they live in and on us—in our gut, our pores, our eyelashes, you name it. There isn’t a crevice, cranny, or fold on the inside or outside of our body that isn’t inhabited by tiny microorganisms ranging from fairly large mites to microscopic microbes.

 

Our Relationship with Microbes: It’s Complicated

Research on the microbiome with respect to bacteria has come a long way in the last century. We’ve advanced far enough that we’re on much friendlier terms with them, but there’s still a lot we don’t know. However, we do know that most of them are helpful, or symbiotic, and even the bad ones, or pathogens, have their good days.  

For example, Staphylococcus epidermidis, a common bacteria found on healthy skin, is usually commensal, which means it works cooperatively with others to keep its host (us) healthy. The most notable way it does this is by releasing antimicrobial peptides (AMPs), which inhibit pathogenic invasion. But Staph epidermidis also surround plastics such as catheters in hospitals, and in that context it has come to be tarred with the brush of pathogenicity. (Seems to me they are just trying to be helpful and repel a foreign invader, but hey, I’m sure it annoys the hospital staff!)

I make this point to illustrate that over the past few decades there’s been a paradigm shift of major proportions when it comes to understanding the role microbes play in our lives. We’ve moved from the old “germ theory” of disease that dominated the 20th century, in which microbes were indiscriminately regarded as dangers to be exterminated, to the “balanced microbiome” theory of health that informs the 21st century. We now understand that our very survival depends on supporting diverse populations of microorganisms, and more efforts should be directed towards befriending the good ones than alienating the bad ones. When the microbiome is in balance, health follows.

 

The Largestand Most OverlookedPart of the Microbiome? Viruses.

The heading above bears repeating, but that said, we are only a tenth of the way there when it comes to understanding the microbiome. Mites and bacteria are just the tip of the iceberg when it comes to microorganism populations. In fact, in the human holobiont—the term used to describe the phenomenon of species living together as a single entity—human cells are outnumbered 10-fold by bacteria and 100-fold by viruses. The human microbiome contains about 38 trillion bacteria—and about 380 trillion viruses. (1)

This means microbiologists have a lot of territory left to chart! We are only just now uncovering some of a virus’ most basic features. You may be wondering why it’s taken so long for this to happen, but it’s only very recently that we’ve had the sophisticated tools necessary to decipher what a human virome actually looks like. 

 

Here’s what we do know:

  • Viruses are highly abundant in most environments. One liter of seawater contains 10,000,000,000 or 1010 virus-like particlesthat’s approximately ten times the number of bacteria found in the same selection. (2) 
  • Viruses can be found nearly everywhere in the biosphere, totaling an estimated number of 1.2 × 1030 in the open ocean, 2.6 × 1030 in soil, 3.5 × 1031 in oceanic subsurfaces, and 0.25–2.5 × 1031 in terrestrial subsurfaces.
  • There are 10 times as many viruses as there are microbes in a human microbiome: 38 trillion microbes to 380 trillion viruses.
  • Viruses have an enormous impact on our health and well-being in ways we are only just beginning to appreciate.

 

So what does this mean? It means that we need to stop being strangers with viruses—that in fact, our lives depend on it. So let’s start with the basics.

What is a Virus?

A virus is a simple thing; so simple, in fact, that a common question people ask is whether a virus is even alive. Technically it isn’t, because although viruses “live” in us they can only replicate inside the cells of their host, which can be an animal, plant, bacterium, or fungus. 

An individual viral particle, called a virion, consists of genetic material, either RNA or DNA, enclosed in a protein coating. It is a far simpler structure than a bacterium, and because it can’t exist on its own, it is certainly not alive in a conventional sense.

The influenza virus mutates at a high rate, which is why flu is a problem every year.

Many viruses are enveloped viruses. Their protein coatings (capsids) are enclosed by an outer membrane that comes from material co-opted from the infected host cell’s own membrane. As the new virion buds out from the host cell, it is wrapped by the cell’s bilayer membrane, which can carry with it any protein that happens to be embedded in the membrane at the budding site. The newly “hatched” virion can then start a new cycle of infection by fusing its cell-derived envelope with the cellular membrane of an uninfected cell.
 

The Viral Infection Cycle

Viruses are skilled break-in artists and hijackers. In order to replicate, they must first get inside the host cell, where all the necessary machinery to make new viruses is found. Viruses are host specific; some of them have a broad host range and can infect multiple species.

  1. The Break In. Viruses identify their host by a lock-and-key arrangement—there are specific receptor molecules on the host cells corresponding to similar proteins present on the surface of the virus. The proteins on the virus attach to receptors on the cell, working like a lock and key.
  2. The Hijacking. Once a virus breaks into a cell, it hijacks the cellular processes to produce virally-encoded protein that replicates the virus’ genetic material. Each molecule serves as an instruction book, with genetic information providing instructions that tell a cell what to make and when to make it. Once inside, the virus sends a message, and one message only, to the cell: make more viruses. Eventually the host cell dies, spewing out new viruses that go on to attack more cells.

 

Viruses and Humans: A Lethal Relationship Mediated by Science

Viruses kill thousands of people every day. In 1918, flu caused more deaths than the whole of World War One. In 2002, three million people died of AIDS, which is caused by human immunodeficiency virus. Before AIDS the great killer was smallpox, which killed untold millions until a scientist called Edward Jenner invented vaccination in 1796 (and for years afterward until the vaccine was widely available). Smallpox has virtually disappeared from society, as has another great viral scourge that terrified everyone in the twentieth century: polio. 

As a kid growing up in the 1950’s, I remember that every summer brought with it the terror of polio. All of us personally knew people—sometimes our friends—who were paralyzed, crippled, or dead due to this terrible disease. Public pools and playgrounds were closed because we didn’t know where it would strike. At its height polio caused more than 15,000 cases of paralysis a year in the U.S. I can still see in my mind the famous picture in Life magazine of row upon row of kids in iron lungs; this picture alone was enough to wring grief for the unfortunates, and terror for our own safety, in every child’s heart. In short, polio was by a long shot the most feared disease of the twentieth century. Then along came one of the world’s great scientist-heroes, Dr. Jonas Salk, who developed the polio vaccine. 

What happened next is an inspiring example of how people dedicated to the common good can work together to vanquish a common enemy. Dr. Salk refused a patent for his work, saying the vaccine belonged to the people and to patent it would be like “patenting the sun.” Wow. Then leading drug manufacturers vied with each other to make the vaccine available free of charge. Double wow. I remember the day my father drove us in our Chevrolet (the size of two Smart cars) to the parking lot that had been set up to dispense sugar cubes dosed with the vaccine. Waiting our turn in a long line of cars, we were eventually handed a sugar cube—one each for the three of us—and voila! No more threat of polio for either us or the millions of others who were privileged to participate in this grand exercise in humanitarianism. More than 400 million doses of the vaccine were distributed between 1955 and 1962, reducing cases of polio by 90%. (3)


    Vaccines

    For the most part, our immune systems do the work of protecting us from disease. When we are exposed to a virus, or parts of one, the body responds to the infection with a fever, runny nose, and so on. As we recover, our immune system stores information about this virus in its immunological memory. When we next encounter this particular microorganism, our immune system can draw upon its repertoire of antibodies, launching the ones it needs to defend us from attack. 

    Vaccines can contribute to immunological memory, heading off the necessity of the individual having to do all the work of contracting the infection, fighting it off, and creating the antibodies. In the case of horrible diseases like polio and measles, this is definitely the preferred route. Vaccines can consist of either live or attenuated (weakened) viruses, inactive or killed versions of the virus, or subunits, which are highly specific parts of the virus.

     

    The Future of Viruses and Human Health: Bacteriophages

    While it may look as if viruses are always the bearer of illness, we have to remember that this is how we once regarded bacteria—that they were all just germs that we needed to eradicate. Further investigation revealed the helpful side of bacteria. They digest our food and they repel invaders, among other important tasks, and we literally cannot live without them. 

    So what about these viruses, which are ten times more numerous than bacteria? Sure, we hear about the dangerous ones, like the ones that cause the flu or the common cold, along with the more sinister ones like Ebola with its 50 to 90% fatality rate, or the rabies virus which jumps over to your nerve cells and moves up to the brain, and now there’s the latest existential threat presented by Covid-19. But are all viruses bad? Or can we infer from our experience with bacteria that there’s more to the virus story than just as carriers of disease? 

    This question offers a smooth segue into the realm of bacteriophages. Besides looking like adorable aliens, what do they do? The answer is we don’t really know, but it looks like some of them at least might be batters on Team Human.

    The human body is a breeding ground for bacteriophages, or “phages” for short, though despite their abundance, we have very little insight into what all they or indeed any of the other viruses in the body are doing. We do know that some bacteriophages can attack bacterial infections inside our bodies. There are recent anecdotal examples of using phages successfully to treat life-threatening infections from bacteria resistant to most if not all available antibiotics. This treatment is known as phage therapy. (4)

    Phage therapy could prove very useful in an era where resistance to antibiotics and multidrug-resistant (MDR) infections has skyrocketed. Phage treatments are in their infancy, and development is hindered by inadequate information as to how phages behave in the human body, as well as the unforeseen consequences their introduction may have on the human host. For these reasons, phage therapy remains heavily regulated, and at the current pace of research it may be many years before phages are used routinely as anti-infective treatments. 

    Nevertheless, our successes with putting bacteria to good use, as in probiotic therapies which are now quite common, may help to moderate our attitude towards viruses. The viruses that have co-evolved with us for millennia are not only part of our past, they are a part of the future of human health. And not always in a bad way.

    Viruses and Skincare

    Viruses are tremendously important with respect to skin health, but we unfortunately know so little about them as yet that it’s difficult to assess their overall impact. Are viruses, like bacteria, mostly commensal with a few bad actors? That’s a question we have yet to answer. However, we do know it only takes a few bad actors (or even one!) to overwhelm a system, so virulence is one of the topics we need to address first. When it comes to viruses we have a great deal to learn, and our studies will occupy us for many years to come. We at Marie Veronique (of course!) would like to jumpstart studies into how viruses affect skin. Skin research usually lags behind, but we feel strongly that skin health is important and should not be overlooked.

    In the meantime we do know that the skin has natural systems in place to maintain its own health. Your best bet is to take measures that support your skin’s protective barrier layer, like not stripping the skin, using microcidal rather than microstatic preservatives in your skincare, and enhancing barrier function with micronutrients.

     

    Before You Go...

    I’m always thinking about the big picture when it comes to recent news from the science world, and I think it’s clear that Covid-19 is a watershed moment in world history. What do I mean by that? Read on…

     

    Comorbidity, Coevolution, and Covid-19

    Humans in some countries are doing a better job at containing the virus that causes Covid-19 than others. Those countries strictly enforcing shelter-in-place rules appear to be coping better than those that aren’t. Wearing masks might contribute towards limiting the spread of the virus, which we now believe is through droplets and surfaces. The principal mode of transmission is thought to be respiratory droplets, which may travel up to six feet from someone sneezing or coughing—hence the social distancing rule of six feet. Frequently washing hands also helps as it slows down the spread of virus picked up from touching contaminated surfaces.

    People have also benefited indirectly from shelter-in-place regulations. Our air quality has improved worldwide due to a massive reduction in burning of fossil fuels. Since it has been established that Covid-19 becomes more lethal when there is comorbidity, i.e., an underlying health condition such as heart disease, hypertension, or respiratory problems, it could be argued that pollution leading to respiratory insufficiency makes air pollution comorbid with Covid-19. If there is a correlation, then we should expect to see cleaner air resulting in lowered mortality rates. This might have happened already in China, but tracking death rates as coal fired factories go back online would also be instructive. If true, then it would be a case of short-term actions leading to unexpected positive consequences. And it would also indicate that we should seriously consider making these short-term actions long term.

    For the sake of argument, let’s assume that our short-term actions are leading to unexpectedly good consequences—a cleaner environment, more time to spend with loved ones, a chance to read all the classics over again, the demise of global capitalism, etc. If we collectively reach the decision that the new normal should be permanent because business as usual no longer works for us (that in fact it was killing us without us realizing it), then we need to look for new models of social behavior.  

    The good news is that we need look no further than our own microbiomes. The inhabitants of our holobiont—bacteria, mites, and, yes, even viruses—work cooperatively to keep their host thriving and well. They understand that their host’s health is intimately related to their own well-being.

    Now let’s enlarge the microbiome picture by imagining that we are microorganisms inhabiting the planetary holobiont. We human microorganisms have set up colonies everywhere—the desert, the mountains, Antarctica, tiny but expensive apartment-cells in heavily populated urban areas, etc. We’re proud that our fiendish cleverness and opposable thumbs have allowed us to expand into some incredibly inhospitable territories. Sadly, our zeal for real estate development has, in more ways than one, gotten out of hand. We’re at the point now where we’ve managed to pollute every single one of our living spaces, and our planet host has gone from welcoming us as co-inhabitants to regarding us as pests. From Mother Earth’s point of view, humans are pathogens who have outstayed their welcome. What accounts for her change in attitude?

    For starters, fossil fuel burning has driven CO2 gases in the atmosphere past the safe limit of 350 ppm to 415 ppm. Rising temperatures correlating almost exactly with the release of greenhouse gases have unleashed tornadoes, hurricanes, floods, and drought in our direction—all warnings we’ve chosen to ignore. And then one day a creature too small to see arrived to give us a new set of instructions. Stop polluting or die. By some miracle, we stopped to listen. By some miracle, we heard. We are at this historical moment taking the steps needed to stop acting like pathogens. It’s encouraging to see that humans can so dramatically and quickly modify their behavior. That’s a huge paradigm shift right there.  

    Since we don’t really know what viruses are doing, I might as well go out on a speculative limb here and suggest that viruses play a more important role than our limited imaginations have allowed us to conceive of. What if they co-evolved with us for a reason—not simply to kill us but also to help us survive? What if they contain information guidelines that will help us moderate our bad, i.e., pathogenic, behavior? If so, it will be up to us to heed the messages they are sending loud and clear. I can see them waving their tiny banners now…  “You don’t tolerate pathogens in your human microbiome—Mother Earth doesn’t tolerate pathogens in hers.” “Pollution is your comorbidity, we take care of the rest.” “Modify or die.” “Competition is dead. Long live cooperation.” “Tune in or drop dead.” 

    The changes we are in the midst of making must become permanent. We’ve made a good start, so let’s not stop now. 

    For further reading, I recommend Jane Goodall’s article on Slate.com:
    Covid-19 Should Make Us Rethink Our Destructive Relationship with the Natural World

     

    1. Metagenomics and Future Perspectives in Virus Discovery. Current Opinion in Virology, Volume 2, issue 1. 2012, pgs 63-77 
    2. O. Bergh, K.Y. Borsheim, G. Bratbak, M.HeldalHigh abundance of viruses found in aquatic environments. Nature, 340 (1989), pp. 467-468 Nature, 340 (1989), pp. 467-468
    3. Jonas Salk and the Polio Vaccine, Who2 blog, March 28, The Conversation, Carl Kurlander
    4. Development and use of personalized bacteriophage-based therapeutic cocktails etc. Antimicrobial Agents and Chemotherapy, Robert T. Schooley et al

     


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