Going viral: What happens in a virology lab?

Why do we study viruses?

Viruses don’t have brains, but they do have an evolutionary “goal” – they want to spread their genomes to as many cells are possible. Their entire biological machinery is based around this pursuit, including their extraordinary ability to adapt to keep spreading.

This might not have a major effect on the body they are using as a host – for example, warts are annoying and a bit sore, but people rarely die from the Human papillomavirus (HPV) that causes common finger warts.

But other viruses, like Ebola, can cause symptoms that lead to death.

According to Farhid Hemmatzadeh, an associate professor of virology at the University of Adelaide, viruses are a big part of nature.

“They do not only cause diseases in humans and animals – they cause disease in plants and the other microorganisms. All the organisms.

“Even bacterial cells, meaning other microbes, have their own viruses. They get sick, and they will die because of the viruses.”

This can make them incredibly dangerous, as we can see from pandemics past and present. If the viruses that kill also spread quickly, we need to have enough knowledge to fight back against them – or, ideally, prevent an outbreak in the first place.

“There are obviously a lot of reasons for studying viruses,” says Ross Balch, a PhD student at the University of Queensland’s Faculty of Medicine.

“Viruses can infect humans, and in fact throughout history we’ve seen viruses do untold health damage to humans. In order to come up with treatments for viruses for vaccines, we need to understand how they work, and that involves working with viruses.”

Viruses will continue to change and mutate to get better at spreading, so virology is an essential part of understanding our world.

“We need to know how they live, how they amplify and how they produce diseases,” says Hemmatzadeh.

“That’s why virology is a big part of biology in general, and a big part of the infectious diseases studies in human animals.”

But viruses aren’t all bad news.

“Viruses can also be extremely useful in healthcare,” says Balch. “There are certain viruses that infect bacteria, and they can actually be used as a treatment against bacteria.”

Viruses can also be used in other research; for example, molecular geneticists can use viral vectors – that is, modified viruses with a bit of DNA under study – to deliver DNA into bacteria cells to see how a gene would work or make protein. Viruses, or viral mechanisms, have been common in molecular biology since the 1970s.

 

Are viruses studied in response to an outbreak or in preparation?

Both. Sometimes a new virus might arise spontaneously, so a lot of research will happen after it has appeared.

But some viruses we suspect may one day turn nasty, so research is directed towards preventing a huge impact when it inevitably mutates.

“Had we been working on coronavirus more, we would have been more prepared for the current pandemic,” says Balch.

“For instance, a lot of treatments that started development lost funding after it had been five years or so [after the] last coronavirus outbreak. But then a new one came along, and we weren’t prepared.

“And that’s really what it comes down to – we need to be prepared for dealing with them if they break out into the population to create treatments and create vaccines.”

 

What technologies and techniques are used in virology labs?

First of all, you need a bit of the virus you are studying. This comes “from disease samples that are submitted to the lab, or [collected for] research in our lab,” says Hemmatzadeh.

These samples aren’t very useful for research in their initial form, because they contain all sorts of other things, like blood, snot or saliva. First the virus needs to be taken out of the sample.

“The golden standard and the traditional method that is established in every virology lab is virus isolation,” says Hemmatzadeh.

“That means we work with the live viruses and use cell culture techniques, or the chicken egg technique, to isolate, propagate and study the viruses. They are applicable only for the live viruses in the majority of the cases because they have their own risks, and they need very, very specialised cell culture facilities.”

Viruses require a host because they are made of fragile RNA, so they are put into special cells for use in other molecular biology techniques. Since the cells now hold a viral genome, they are perfect for genetic analysis.

A lot of virology labs use techniques from molecular biology, such as PCR – a technique that helps researchers identify certain genes that might be common in a virus, which can be followed by genomic sequencing to either identify the genome of a new virus, or to track small genetic mutations that might make a virus more problematic.

The individual properties of a virus can also be studied to understand how a virus interacts with the body. For example, this can help identify viruses that might spread very quickly or learn exactly how a certain viral protein can break into cells.

Any type of virus treatment – including vaccines – needs to be tested thoroughly before it can be taken to trial. This involves multiple steps, where a virus is isolated, genetically sequenced and subjected to multiple tests in vitro (i.e., in Petri dishes or test tubes) before it can even be tested in an animal model.

“The third method that we use in a virology lab [is called] serology, which means we detect antibodies in the body of humans or animals, “says Hemmatzadeh. “In my lab, mostly animals.

“We work with animal viruses, and we detect antibodies to viruses in the blood of animals. We [can] say, ‘those animals were exposed to this virus’, or ‘the animal is positive for this virus’, or ‘those animals were negative for this virus’.”

They also use a technique called western blotting to separate viral proteins in a jelly-like substance based on size, and detect which proteins are present in the sample, what the structure of the protein is and how it behaves.

This is just a sample of what goes on, but these are all fairly standard molecular biology techniques that are also used in other labs, from genetics to fertility to plant research labs.

 

Does a virology lab focus on just one type of virus?

There are a lot of viruses in existence – perhaps so many that all the zeros can’t be put into this article, so here’s a rough estimate: a quadrillion quadrillion (that isn’t a repeated word!) – 1,000,000,000,000,0001,000,000,000,000,000. Of course, not all of those viruses affect human health.

But labs can definitely study more than one, because there is a lot of crossover knowledge in terms of how viruses behave.

“It totally depends on the research focus of the lab [but] it is almost impossible for one lab to be focused on all viruses,” says Hemmatzadeh. “For example in my lab, in terms of the research, we mainly focus on influenza and the Newcastle disease virus for birds. And, on the other hand, we [also] focus on the Parvoviruses and pet viruses in general.”

 

How do you grow, and keep, a virus?

Viruses require a host cell to stay alive.

“Viruses are extremely fragile,” says Balch. “One of the interesting things with working with them is that it’s actually incredibly hard to grow viruses, because they need very specific conditions – because they are so easy to kill. This the reason why washing ethanol on your hands is so good at getting rid of coronavirus.”

To combat this, viruses are put in special cells that can be grown on a Petri dish. The cells are specially designed to grow in labs, and often require minimal effort to keep alive – just a bit of sugar or nutrients in the form of a jelly-like media.

The cells also like growing at the right temperature, so they can be forced to start or stop reproducing quite easily by turning the temperature up or down.

When a virus is not being used, it is stored in facilities at -80°C, or in liquid nitrogen, which at -196°C is so cold that life can’t really exist – instead, the virus remains in a dormant state.

“There’s actually a register of those nationally in Australia,” says Balch. “If you’re working on something that is level three, we know every single level three organism. We know where that is because we keep that in a register.”

 

What biosecurity measures need to be adhered to?

There are very strict rules about biosecurity in Australia, and most places around the world, when it comes to viral control in labs.

“Essentially a lot of the precautions that you need for bacteria [focused-labs] are the same,” says Balch.

“A lot of viruses are actually quite hard to spread when they’re not being spread by the host. And in fact, a lot of the time bacteria [which doesn’t need a host] are actually a lot more difficult to work with than viruses for that reason.”

Both bacteria and virus labs have multiple tiers, or levels, of biosecurity, depending on how dangerous they are.

Viruses such as the common cold, or things that can’t really spread, fall under level two, where all of the laboratories have a buffer room that is a slightly higher pressure than the labs. This means that when the door is opened, air always flows from the outside into the lab, instead of the other way around. Then, even if a virus is in the air, it can’t flow out of the room.

“But viruses like, say, coronavirus – especially the novel ones like SARS, and obviously the current coronavirus – they would be worked [on] in level three lab [which] has an extra level of [protection],” explains Balch.

 

How do you get rid of a virus when you are done?

One of the most common forms of biological control in labs is autoclaving. This involves blasting the material with high-pressure steam at around 121°C for at least 20 to 30 minutes. It’s kind of like a big pressure cooker designed to kill living biological material.

At this point, Balch explains, “Every single virus known to society will essentially die and be intransmissible at that stage. It gets ripped apart, essentially, and it can’t do any damage at that point.”

Autoclaving isn’t just for viruses, either – it is used to sterilise space rocks and hardware being sent to Mars, destroying genetically modified cells and plants, and cleaning medical instruments.

Some viruses may be heat resistant, however, so once they are autoclaved, they also are post-processed in special facilities, just to be certain.

“It’s the same process, but it’s just as an extra step of care taken in that particular case,” says Balch.

 

Can you artificially make a virus?

Technically yes – it is quite common to engineer things to make them easier to work with in molecular biology, but the question is quite complicated because it sounds so scary.

Working with live viruses is a lot riskier than working with dead viruses or the individual components (like proteins), but researchers still need to see how those individual components might work in vivo (that is, in real life). To do that, they often need to be engineered or genetically modified so that a single component can function without the rest of the virus.

“Sometimes we can kill the live viruses, but still we can work with them,” explains Hemmatzadeh.

“The vaccines contain the virus part – viral particles – but they are not alive. That’s why it is applicable for the vaccine, it is applicable for the viral proteins, and it is applicable for the viral genetic materials.

“We can extract those components and analyse them and say, run the diagnostic tests, or run the research projects [using] them.”

When it comes down to it, modified viral components are often much safer and easier to use in the lab than a live virus.

“In the majority of the cases, we work with the virus materials, mainly genetic materials or viral proteins,” says Hemmatzadeh.

“In this case, we do not work with the live viruses.

“That’s why the biosecurity level for that particular virus [component] is the same as any molecular biology lab.”

Viruses can also be synthesised because they are made of RNA and have a nucleotide sequence, so they can be made in basically the same way as other synthetic DNA. Put simply, this involves precisely building a sequence from a previously written genetic code, like following the instructions of a big Lego tower.

This isn’t much different from synthesising other molecules – like salicylic acid in aspirin – but it does technically mean that changes can be made to the RNA code so it has different properties. However, it mostly means you either don’t have to go through the rigmarole of getting more product when you can just make it, or you design a protein sequence instead of spending time selectively breeding it. There are many applications of genetically modified viruses beyond the lab, too, such as in cancer treatments, vaccine development, gene therapy and improved plant health.