Auburn disease ecologist discusses emerging novel viruses, how loss of wildlife habitat may play a role

Sarah Zohdy, assistant professor of disease ecology in Auburn University’s School of Forestry and Wildlife Sciences and the College of Veterinary Medicine, discusses what leads to the emergence and spread of novel viruses; the major threats to human and animal health; and how the spread could be rooted in the loss of natural, wildlife habitats.

How often does the world see epidemics? Pandemics? What is the difference?

Epidemics occur constantly around the world. At its core, an epidemic occurs when a disease has an R0 greater than one. What does that mean? R0 is a key epidemiological indicator, a number that represents the number of individuals a single infected individual can infect. For example, an R0 of one means every infected person will infect one other person. An R0 of two means infected individuals will infect two people, etc. R0 is calculated based on social contact rates and transmission patterns to predict how fast and far pathogens can spread. An epidemic is defined as an infectious disease that has an R0 of greater than one, meaning it will spread. An epidemic will affect many people at the same time in a community or region. A pandemic is when an epidemic may affect many people at the same time in a much larger region, for example an entire continent or the whole world.

What leads to emerging viruses?

This is a very good question and a very complicated one. As long as there have been humans, there have been viruses. Viruses use our cellular machinery to replicate, leaving genetic traces of ancient viruses, or endogenous viral elements (EVEs) in our genome. So you can look at the history of viruses in our own DNA.

In recent decades we have seen an increase in the emergence of infectious diseases, and the majority of those have origins in wildlife. The true underlying mechanisms that drive this remain unclear (our team from Auburn developed a hypothesis about how this happens), but we know that habitat loss is associated with the emergence of infectious diseases, and human travel and movement and population growth can help facilitate how quickly these emerging pathogens may spread. Of emerging infectious diseases (EIDs), the majority are caused by viruses.

There are several different types of pathogens, like parasites, bacteria, fungi, prions or viruses. Each of these organisms has a unique genetic make-up. For example, bacteria, parasites and some viruses are made up of DNA; prions are made up of misfolded proteins and no nucleic acid (no DNA or RNA); and viruses come in multiple forms and configurations and are typically described based on their molecular and morphological structures. Viruses are unique because they do not have their own molecular machinery to replicate by themselves. They are often described as a piece of nucleic acid (DNA or RNA) wrapped in a protein coat. They invade host cells and take over the cell’s machinery, having the ability to multiply very fast, which means they have the ability to evolve much faster than other pathogens (we have a figure of null mutation rates of different pathogens in this paper). There are DNA viruses and RNA viruses, and RNA viruses are the ones we see emerging most frequently. The reason for this is RNA viruses don’t have a DNA polymerase. This is essentially a gene-editing mechanism that can catch and remove mutations. Without DNA polymerases and with a very high replication rate, RNA viruses end up mutating much faster than any other known pathogens, meaning that they can essentially adapt to very different host environments rapidly, even if just by chance because they have accumulated enough viral mutations. This happens so fast that even within an individual host RNA viral genomes can differ slightly, and across populations they differ even more so.

All of this is to say that RNA viruses can adapt much faster and better to new host environments, whether that is in a new host species, like humans, or into a vector species, like ticks and mosquitoes. So if you look at the trends in emerging infectious diseases over the last few decades, the majority have been RNA viruses (Ebola, Marburg, Hendra, SARS, MERS, Zika). There are many hypotheses about why we have seen more emerging infections in recent decades. Several hypothesize that an increase in human-animal contact facilitated by habitat loss and human encroachment into natural habitats has facilitated increased human contact with pathogens from animals that would not have been encountered previously, and global travel has allowed viruses to emerge out of even the most remote locations.

What is the best way to prevent, or slow down, novel viruses?

This is a really critical question and one that, unfortunately, we do not have a clear answer to it. We are really at an incredible time scientifically where we can learn more about the genomes and biology of new pathogens (viruses) in hours than it used to take teams of people decades to learn, but we are still learning about new viruses. In order to predict, prevent or slow down viruses, we have to understand the basic process of spillover from one animal to another.

A distinction should be made between the different stages and types of cross species transmission: a) pathogens moving between species (zoonotic spillover), b) pathogens moving between species and subsequently causing disease then stopping there (humans as dead-end hosts), c) spillover causing disease and subsequent pathogen transmission between individuals of the new species. These three are different things. Spillover events likely occur constantly. We are regularly coming into contact with pathogens from different species, but our immune system typically does a great job of clearing these foreign organisms. We live in a world of microbes, and the immune system is an amazing thing because a very, very small percentage of known viruses cause symptomatic disease.

Can outbreaks reoccur in the future?

The short answer is yes. Not only can epidemics continue to occur in the future, they will occur. Every step that exists from pathogen spillover to infection to disease to community transmission presents an opportunity for an intervention point and there are scientists working at each of these intersections to help minimize impact. That can seem overwhelming, but science is in such an incredible place right now. We can advance research progress at a rate previously unheard of. Rather than focusing on the fact that unknown pathogens will continue to emerge in human populations, it can be beneficial to examine strong public health successes that have done so well at preventing epidemics/pandemics that most of the world did not even notice.

Some incredible research has been done on influenza, specifically influenza A, which is the zoonotic (of animal origins) type of virus that causes the flu. While influenza may not sound very unique or exotic, it is one of the best examples of an emerging infectious disease. As an RNA virus, influenza viral variants emerge quite frequently following moving back and forth between species, often between humans and domesticated animals (H1N1, H5N1, H7N9), which is why there are slightly different flu vaccines every year. Influenza viruses are known for their ability to spread rapidly and lead to morbidity and mortality, so a lot of work has gone into protecting humans from the next influenza pandemic. Scientists have been trying to keep ahead of the curve and have largely done so successfully with flu. Rapid testing in health clinics allows for on-site diagnosis and confirmation. When poultry get sick or die due to highly pathogenic avian influenza strains, a warning signal of potential emergence, culling infected poultry populations can halt the new strain before it is too late. Science is at an incredible place and pace now where we are racing to keep up with rapid viral evolution (somewhat successfully!) and flu vaccines are great evidence of this. Every year that we do not see an influenza pandemic is a testament to the incredible science and research that has gone into being on high alert for this constantly emerging infectious disease.

What concerns you most about novel viruses?

This is a challenging question and I wouldn't necessarily say I am concerned about novel viruses themselves, but rather the potential impact they may have. I think it is important to distinguish the viruses themselves from the disease symptoms they may lead to. As mentioned above, only a very, very small proportion of new viruses cause disease, and, of those, even fewer lead to epidemics and pandemics. As a biologist, I think about the constant evolutionary race between viruses evolving and  immune systems evolving to combat them, on and on ad infinitum. So from that perspective, novel viruses are inevitable and are just organisms which coexist with us and continue to evolve and change, just as other organisms on our shared planet do. What is concerning are the diseases novel viruses can cause which we are unprepared for.

Another important thing to consider is the indirect impact of EIDs. Data exist that show that when epidemics occur and health care capacity is maxed out as a result, there are indirect costs or “hidden tolls” in morbidity and mortality. For example, following the 2014 Ebola outbreak, a significant increase in malaria was documented (Science Direct and Nature) because of the shift in health care capacity focusing on the epidemic. So ensuring the strength and capacity of existing health systems is critical when EIDs appear. Without this, the indirect morbidity and mortality due to other infectious diseases and underlying conditions can well surpass the burden that results from the epidemic/pandemic.

I do think it is important to rethink the concept of being concerned with the emergence of novel viruses themselves, which are inevitable, and instead think about our response capacity to deal with the epidemics and pandemics viruses will lead to in the future.

About Sarah Zohdy:

Sarah Zohdy is an assistant professor of disease ecology in Auburn University’s School of Forestry and Wildlife Sciences and the College of Veterinary Medicine. Her research interests include parasite-host dynamics, primatology, wildlife disease ecology, vector-borne diseases, public health and conservation biology. She focuses on the ecological and evolutionary drivers of disease in human and animal communities. Her team works in field sites all over the globe using a One Health approach to evaluate how anthropogenic disturbance influences infectious disease dynamics that threaten human and wildlife health.