Zoonoses, COVID-19, and the EPA - what's the connection?

Principal Scientist and Acting manager of our New Organisms team, Dr. Tim Strabala, explains how zoonoses operate, and how these diseases relate to the work we do.

Photo of a collection of animal noses

Not to be confused with cute noses on exotic creatures, zoonoses are diseases that can be transmitted between animals and humans (and vice versa). COVID-19 is just the latest and most prominent zoonosis.

COVID-19 is a zoonotic Coronavirus – but it’s not the first

As I'm pretty sure we all know by now, COVID-19 is caused by a Coronavirus, specifically SARS-CoV-2. But this is not the first zoonotic Coronavirus that has infected people in recent years, and had the potential to go viral (but definitely not in a good way), and cause a pandemic.

Back in 2002-2004, we dealt with SARS-CoV (the virus formerly known as SARS, which actually is the name of the disease it causes), and outbreaks of MERS from camels back in 2012, 2015, and 2018. Although these viruses are zoonotic, their animal origins are still a bit murky. SARS-CoV is thought to have possibly originally come from bats and possibly transmitted to civets (a cat-like creature), and then to humans. Similarly, although humans appear to have contracted MERS-CoV from camels, the original source may have once again been bats.

But Coronaviruses aren't the only kinds of zoonotic viruses that you can get. There are many different ways in which these little replication machines have adapted to hijack your cells for their own ends. And maybe a bit surprisingly, not all of these zoonotic infections are bad. I thought that I'd give a couple of examples from some recent EPA approvals for the environmental release of medicines¹ containing genetically modified viruses to show you what I mean.

¹NB: We can only give approvals for medicines that are, or that contain, a new organism (including GMOs) as defined in the Hazardous Substances and New Organisms Act 1996. EPA approvals are not for the use of the medicine in patients, but rather for the release of the new organism into the environment.

Arboviruses, and an EPA-approved vaccine

The first type of virus that I'd like to tell you about are the Arboviruses, shorthand for arthropod-borne, meaning simply that they are generally transmitted by mosquitos or ticks that bite us. The virus goes along for the ride in the saliva of the animal to get into our bloodstreams.

A recent approval that EPA granted was for a vaccine against Japanese encephalitis virus (JEV). JEV is an arbovirus belonging to a group of related viruses known as flaviviruses, with "flavi" being Latin for "yellow", and the class is named after Yellow fever virus. Also in this group are many other really nasty viruses, such as Dengue fever virus, West Nile virus, and yes, even Zika virus. All of these viruses are transmitted either by mosquitos or ticks. Their non-arthropod animal hosts can vary, but are often waterfowl, bats and other species.

Importantly, JEV also infects horses and pigs. Like humans, horses can get disease from JEV, but don't pass it on, because the amount of virus in their bloodstreams (called viraemia) is too low for mosquitos to pick it up. Horses are thus known as 'dead end' hosts.

However, pigs develop high levels of viraemia, and since humans are generally in closer proximity to pigs than wild animals, they are known as amplifying hosts, and are usually where mosquitos will acquire the virus before passing it on to humans. Fortunately, humans themselves are dead-end hosts, and so it doesn't pass human-to-mosquito-to-human.

Because of the horrifying effects caused by these viruses (encephalitis is inflammation of the brain), they've been the focus of vaccine development for more than 80 years, starting with the Yellow fever virus vaccine. The vaccine that the EPA approved is a genetically modified live-attenuated (capable of very limited replication, but incapable of causing disease) virus that uses the "backbone" of the Yellow fever virus vaccine, while presenting the surface proteins derived from another live-attenuated JEV.

While JEV thankfully isn't something you can catch in New Zealand, the vaccine is now available to travellers and aid workers who go to regions where JEV is endemic.

EPA news article about the approval of the JEV vaccine

How cows spurred the very first vaccine

In contrast, coming from the "zoonosis isn't always bad" category is the Vaccinia virus. This virus generally infects cows, but it doesn't really cause much in the way of disease. This virus caught the attention of the scientific community when it was noticed that dairymaids (yes, this really was a job title 225 years ago!) were protected from catching smallpox, a disfiguring and often lethal disease.

Although no one knew anything about viruses as such at the time, it was well-known that cows, and the dairymaids who milked them, could and did get infected with cowpox, also known as vaccinia (from the Latin 'vacca' for cow).

Vaccinia causes only very mild symptoms in humans, and one of those was the small pustules (every bit as disgusting as it sounds, but still far less so than those caused by smallpox) on the dairymaids' hands that developed when they first started milking cows. Preparations were made from pustule scrapings either from the dairymaids or the cows, and these were shown to confer protection against smallpox to people who received it. This is in fact where the name 'vaccine' came from.

Once the viral causative agents for both smallpox and cowpox were understood, strains of the Vaccinia virus were used to successfully eradicate smallpox from the world by 1980.

In 2015, the EPA approved for use in a clinical trial, a vaccinia virus genetically engineered to replicate preferentially in cancer cells, and also to carry a signalling protein intended to activate the patient's immune system to attack and destroy the cancer cells. That's the thinking anyway.

Last year, the global trial for this virus for the treatment of liver cancer (which included patients at Auckland Hospital) was terminated for lack of therapeutic effect. However, research on similar viruses as cancer therapies for this and other cancers is ongoing.

Approval of a vaccinia virus as a potential cancer treatment in clinical trials

Understanding COVID-19

But back to SARS-CoV-2. How was this particular virus transmitted to humans in the first place? The answer is that nobody really knows for sure yet, and maybe we never will. The route of animal to human transmission of these viruses (including MERS-CoV and SARS-CoV) is not well understood.

As for the animal source of SARS-CoV-2, genetic analysis of the virus shows some similarity to both pangolin and bat coronaviruses, but there is still no match close enough to give confidence of a source, so work is continuing.

Interestingly, testing has also revealed that SARS-CoV-2 can infect domestic dogs and cats. They can also apparently develop disease from the infection, and there were reports that tigers and lions in a New York zoo contracted and became sick with COVID-19. It is thought that SARS-CoV-2 may have been transmitted to the animals by an infected member of the zoo staff.

Meme showing a cat wearing a face mask with the words saying When it's the last of your 9 lives so you've gotta play it safeAnd this is the thing about zoonotic diseases – they can be a two-way street. But not to worry, it looks like dogs and cats might get the short end of the stick relative to us. To date there is no evidence at all that dogs or cats can transmit the virus to humans, but it looks like we may be able to transmit it to them. Now that I know this, maybe the Coronavirus meme isn't quite as funny as I first thought it was.

Play it safe and stay well, everyone. Remember, everything we're doing to stamp out SARS-CoV-2 is working, so please keep doing it!

Further reading

Should pets be tested for coronavirus? - Science magazine website

Covid-19 coronavirus: Tiger at New York's Bronx Zoo tests positive - New Zealand Herald website

Edward Jenner and the history of smallpox and vaccination - National Center for Biotechnology Information website - this paper is a good description of the work of Edward Jenner in the late 1790s in developing and providing the scientific foundation for vaccination:

The Yellow Fever vaccine: A history - National Center for Biotechnology Information website - this work resulted in the only Nobel Prize awarded (to Max Theiler) for the development of vaccine against a virus. This remains the only vaccine in use for Yellow fever virus to this day, although others with more side effects were used in the past.

World Health Organisation information on the 2002-2004 SARS-CoV outbreak - WHO website

WHO information on the MERS-CoV outbreaks - WHO website

The proximal origin of SARS-CoV-2 - Nature Medicine website - this gets very technical in spots, but concludes that it currently can't definitively be shown what host animal first transmitted the disease to humans, or if the mutations making it able to productively infect humans occurred in host animals before it got to humans, or if they were selected for in human infections. What they do conclude, though, is that SARS-Cov-2 was not purposely designed in a lab, but is a product of natural selection and evolution.

About the author

Tim is a Kiwi by way of the USA. He earned a Bachelor’s degree in Chemistry at the University of Colorado, and a PhD in Biochemistry at the University of Wisconsin. After a National Science Foundation postdoctoral fellowship, Tim arrived in New Zealand in 1996. After a 29 year research career, including roles at an Auckland biotech company, and the Crown Research Institute Scion in Rotorua, Tim joined the EPA in 2014, where he is the Principal Scientist and currently Acting Manager of the New Organisms team.