Tag Archives: viruses

Viruses don’t deserve their bad rap: they’re the unsung heroes you never see

The Conversation

Peter Pollard, Griffith University

The word “virus” strikes terror into the hearts of most people. It conjures up images of influenza, HIV, Yellow Fever, or Ebola. Of course we worry about these viruses—they bring us disease and sometimes an excruciatingly painful death.

But the 21 viral types that wreak havoc with the human body represent an insignificant fraction of the 100 million viral types on earth. Most viruses are actually vital to our very existence. No-one seems to stick up for the good guys that keep ecosystems diverse and balanced (although I did recently in a TEDx talk in Noosa).

The sheer number of these good viruses is astonishing. Their concentration in a productive lake or river is often 100 million per millilitre – that’s more than four times the population of Australia squeezed into a ¼ of a teaspoon of water.

Globally the oceans contain 1030 viruses. If you lined them all up they would extend for 10 million light years, or 100 times the distance across our galaxy. Collectively they would weigh as much as 75 million blue whales.

In short, there are a lot.

What are viruses?

Viruses are not living organisms. They are simply bits of genetic material (DNA or RNA) covered in protein, that behave like parasites. They attach to their target cell (the host), inject their genetic material, and replicate themselves using the host cells’ metabolic pathways, as you can see in the figure below. Then the new viruses break out of the cell — the cell explodes (lyses), releasing hundreds of viruses.

The viral cycle. Peter Pollard

Viruses are very picky about who they will infect. Each viral type has evolved to infect only one host species. Viruses that infect bacteria dominate our world. A virus that infects one species of bacteria won’t infect another bacterial species, and definitely can’t infect you. We have our own suite of a couple of dozen viral types that cause us disease and death.

A deadly dance

Algae and plants are primary producers, the foundation of the world’s ecosystems. Using sunlight they turn raw elements like carbon dioxide, nitrogen and phosphorus into organic matter. In turn, they are eaten by herbivores, which are in turn eaten by other animals, and so on. Energy and nutrients are passed on up the food chain until animals die. But what ensures that the primary producers get the raw elements they need to get started?

The answer hinges on the viruses’ relationship with bacteria.

A virus doesn’t go hunting for its prey. It relies on randomly encountering a host — it’s a numbers game. When the host, such as a bacterial cell, grows rapidly, that number increases. The more of a bacterial species there is, the more likely it will come into contact with its viral nemesis — “killing the winner”. This means that no single bacterial species dominates an ecosystem for very long.

In freshwater, for example, you see very high rates of bacterial growth. You would think this high bacterial production would become part of the food chain and end up as fish food. But that is rarely the case.

We now realise that the bacteria actually disappear from these ecosystems. So where do the bacteria go?

The answer lies in the interaction of the bacteria and viruses. When a virus bursts open a bacterial cell its “guts” are spewed back into the water along with all the new viruses. The cell contents then become food for the neighbouring bacteria, thereby stimulating their growth. These bacteria increase in numbers and upon coming into contact with their viral nemesis they, too, become infected and lyse.

Viruses make the world go ‘round

This process of viral infection, lysis, and nutrient release occurs over and over again. Bacteria are, in effect, cannibalising each other with the help of their associated viruses. Very quickly, the elements that support the food web are put back into circulation with the help of viruses, as you can see in the graphic below.

How nutrients are recycled. Peter Pollard

This interaction ensures inorganic nutrients are readily available to algae and plants on which ecosystems depend. It’s the combination of high bacterial growth and viral infection that keeps ecosystems functioning. This explains why we don’t see bacteria in food webs. Viruses short circuit bacterial production passing higher up the food chain so it doesn’t become fish food in freshwater ecosystems.

Most of the food (dissolved organic carbon) that drives the very high bacterial growth in freshwater comes from the terrestrial environment. Indeed, freshwater viral/bacterial interactions appear to be a critical link in carbon cycle between the land and atmosphere.

Soil viral ecology studies lag way behind water research. Viral dynamics in terrestrial ecosystems are complicated as soils can bind and inactivate viruses to limit their ability to infect other organisms. We may well be relying on freshwater processes to complete the global carbon cycle, as shown in the graphic above.

In freshwater, viruses are enhancing the rate of bacterial decomposition whereby complex organic matter is quickly and efficiently mineralised into their simple inorganic components such as carbon dioxide, nitrogen, and phosphorus.

Thus viruses are a critical part of inorganic nutrient recycling. So while they are tiny and seem insignificant, viruses actually play an essential global role in the recycling of nutrients through food webs. We are only just now beginning to appreciate the extent of their positive impact on our survival.

One thing is for sure, viruses are our smallest unsung heroes.

The ConversationPeter Pollard, Associate Professor, Griffith University

This article was originally published on The Conversation. (Reblogged by permission). Read the original article.
 

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Are vaccines making viruses more dangerous?

The Conversation

Dave Hawkes, University of Melbourne

Despite the near-universal acceptance of the benefits of vaccination, some people still worry about risks associated with their use. Luckily, scientists are vigilant about identifying possible risks, so they can be addressed before problems emerge.

Still, people sometimes forget that science is the process by which we arrive at solutions. And they worry about incremental scientific steps that often expose weakness in these solutions.

A recent study published in the journal PLOS Biology, for instance, was presented by some media as claiming that certain vaccines make viruses more dangerous. The research showed chickens treated with its vaccine are more likely to spread a highly virulent strain of Marek’s disease virus, a condition that affects poultry.

The reason was simple: the vaccine used in the study targets Marek’s disease, not the virus that causes it. These types of vaccines are known as “leaky vaccines” because they don’t affect the ability of the virus to reproduce and spread to others; they simply prevent the virus from causing disease.

Marek’s disease vaccines use a non-disease-causing virus to infect cells. This preventive infection stops tumour formation and death when those cells are infected by the Marek’s disease virus.

But the virus can replicate and still produce more virus particle, which can infect other chickens. All Marek’s disease vaccines, since their introduction in the 1970s, have been leaky; they allow chickens to carry and spread the virus without getting the disease.

‘Imperfect-vaccine hypothesis’

The effect of leaky vaccines on how disease spreads is explained by the “imperfect-vaccine hypothesis”. It holds that, without vaccination, a very virulent virus can get into a population and kill infected hosts (people or animals) very quickly – before they have a chance to spread it. This means that the virus will die out very quickly too, as all potential hosts will be dead or immune to it.

A leaky vaccine can prevent the very virulent virus from killing the host, but doesn’t stop that host from spreading the virus to others. This means that a very virulent virus can survive for long periods in the vaccinated hosts. And it can continue to spread in this time, making it less likely to die out.

The PLOS Biology study showed chickens vaccinated against Marek’s disease were more likely to spread the disease to other chickens, than unvaccinated chickens were. The unvaccinated chickens all died in less than ten days – before they could spread the virus.

The vaccinated chickens, on the other hand, were protected from the disease so were able to spread the virus to other (unvaccinated) chickens for weeks and weeks. And they made those chickens immune to the virus in the process.

Marek’s disease, which affects poultry, has a ‘leaky’ vaccine’. David Goehring/Flickr, CC BY-SA

One of the reasons the researchers looked at Marek’s disease in chickens is because it has been getting progressively deadlier. Originally, the disease occurred mainly in older chickens and caused paralysis. But an acute form of the disease emerged in the 1950s and has since become the dominant form. This rather virulent version can kill up to 100% of unvaccinated birds.

Leaky but not sinking

But what does all this mean for the future of vaccination?

Well, the first thing to note is that in this study the vaccinated chickens always had the best outcome. In one experiment, only three out of 50 unvaccinated chickens survived the disease, while vaccination protected the majority of chickens (46 out of 50 survived).

The authors also noted that vaccination has been very effective in preventing deaths in chickens due to Marek’s disease. They said their study didn’t indicate whether vaccination played any role in the development of the serious form of Marek’s disease.

Vaccines prevent disease, even if they’re leaky. But it’s important to note there are currently no vaccines against viruses that infect humans that are leaky. Current human vaccines mimic the body’s own response to viruses.

But yet-to-be-developed vaccines for diseases such as HIV, Ebola or malaria, where humans have been unable to mount an effective natural defence, are likely to be leaky. And even imperfect vaccines for these illnesses would be an enormous step forward.

The possible effect of “leaky vaccines” on how viruses spread is an interesting new observation. But there are a number of other ways by which viruses can change in response to vaccination.

An arms race

One response of viruses to vaccines involves the evolution of viral proteins that allow them to escape the vaccine. This is known as “epitope evolution” and it’s the reason flu vaccines change each year.

Even if a vaccine is effective in preventing a particular strain of virus, other strains may take its place. This was a concern when the human papillomavirus (HPV) vaccine was introduced nearly ten years ago. But researchers have investigated whether any HPV types not in the vaccine have become more common since the vaccine was introduced and there’s no evidence this is happening.

The interaction between viruses and their targets can change over time. In the case of Marek’s disease, the infection has become progressively deadlier. Increased use of broiler chickens, lack of genetic diversity in flocks and high-density rearing may all have played a role in the changes seen in the disease.

The benefits of vaccination far outweigh its risks. And it is research like this that helps medical researchers actively identify possible dangers so we can safely continue to avoid the diseases that terrified our parents’ generation.

The ConversationDave Hawkes is Honorary Fellow at Department of Pharmacology and Therapeutics at University of Melbourne

This article was originally published on The Conversation. (Reblogged by permission). Read the original article.
 

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Explainer: how viruses can fool the immune system

The Conversation

Kim Jacobson, Monash University

The immune system protects us from the constant onslaught of viruses, bacteria and other types of pathogens we encounter throughout life. It also remembers past infections so it can fight them off more easily the next time we encounter them.

But the immune system can sometimes misbehave. It can start attacking its own proteins, rather than the infection, causing autoimmunity. Or, it can effectively respond to one variant of a virus, but then is unable to stop another variant of the virus. This is termed the original antigenic sin (OAS).

OAS occurs when the initial successful immune response blocks an effective response when the person is next exposed to the virus. This can have potentially devastating consequences for illnesses such as the mosquito-borne dengue.

There are around 400 million dengue infections worldwide each year and no vaccine is available. Reinfection of someone who has been exposed to dengue previously can result in life-threatening hemorrhagic fever.

OAS is also thought to limit our immune responses to the highly variable influenza virus, increasing the chance of pandemics.

To understand why OAS occurs, we need to go back to basics about how immunity is formed.

The race begins

When a virus enters the body, a race begins between responding immune cells and the infecting pathogen. The pathogen replicates and finds a target cell or organ that will allow it to thrive.

So, the effectiveness of a response depends on the immune system winning the race to clear the pathogen before it causes irreversible damage to the body.

Immune cells called “B cells” make antibodies. A pathogen such as a virus is a large molecule with different components, called antigens. When a B cell recognises an antigen, it is activated and interacts with other immune cells to receive directions.

Quality control

B cells then set out on two main paths. Some of the cells begin to make an antibody early in the response. But this antibody is often not of sufficient quality to rid the body of the infection.

The B cells that choose the alternate pathway go through a process that improves the quality of the antibody. This strengthens the binding between antibody and antigen. Antibodies are also grouped depending on the way they help eliminate the pathogen.

Some groups are better at clearing viruses and other pathogens. So, the antibody group that is tailored to be most effective at clearing the type of infection comes to dominate the response over this period.

Although the increase in quality of antibody can take weeks, there are two critical benefits. It means the pathogen is cleared. And high-quality “memory” cells remain to provide us with immunity to future infections.

Memory cells

Immune memory cells consist of long-lived plasma cells and memory B cells. Long-lived plasma cells live in the bone marrow and can continuously pump out high-quality antibody, providing a first wave of protection when we’re reinfected with a virus.

This is the same type of antibody that is transferred from mother to a breastfed baby, providing passive immunity against pathogens the mother has previously been infected with. But this level of antibody may not be enough to clear the infection.

This is where memory cells step in. Because memory cells have already undergone quality improvement, they can respond quickly after reinfection to produce a large number of plasma cells secreting high-quality antibody.

Therefore, memory cells can clear the infection much more rapidly than the initial infection. This means the pathogen doesn’t have time to damage the body.

When the quality improvement process fails

The quality improvement process that allows B cells to bind and clear the pathogen more effectively is highly selective to the dominating antigen.

In most responses to infection, this is critical to clear the infection. But in the case of some pathogens, such as dengue, the virus may have variant strains that can fool the immune memory response.

Dengue virus has four major variant serotypes. Within each major variant, one antigen dominates and is targeted by the immune system.

Infection by variant A results in extremely selective targeting towards antigen A. If the body is reinfected with the same variant (A), it can effectively clear the virus.

However, after reinfection by a second variant (in which antigen B dominates), immune memory cells recognise the virus, but they make antibody specific for antigen A, rather than the second variant, in which antigen B is now dominating.

So, antibody is being made but is unable to bind and eliminate the virus. To make matter worse, it appears that any new immune response to antigen B is inhibited by the memory response, although the reasons why this occurs are unclear.

Influenza is a highly variable virus, and these variations each season are why we require yearly vaccinations.

But the role of OAS in limiting our ability to respond to different variants of influenza is still highly controversial. Almost 60 years after OAS was proposed to describe the response to influenza infections, it is still a source of much current research.

How can we avoid OAS?

We need to train our immune system to be more flexible and produce antibodies that can adapt when viruses try to evade the immune system.

To this end, researchers are designing vaccines to respond to multiple variants of pathogens. This has shown promising results and may be the way forward to overcome OAS for potentially life-threatening viruses such as dengue.

The ConversationKim Jacobson is Senior Research Fellow at Monash University.

This article was originally published on The Conversation. (Reblogged by permission). Read the original article.


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