Why do many pandemics start with bats?

Posted by Susan Lubejko on April 9, 2020 in Animals, Immune System, Science in pop culture | Leave a comment

We are in the midst of an unprecedented global health crisis. The new disease COVID-19 has changed many aspects of how we can lead safe and healthy lives. COVID-19 is caused by the outbreak of SARS-CoV-2, a novel coronavirus previously unknown to humans. As health scientists race to find the best testing and preventative strategies, virologists (scientists who study viruses) are also asking a different question: where did this virus come from?

This virus, like many other disease-causing agents, is zoonotic in nature. Zoonoses are diseases that are transmitted from animals to humans. A recent study comparing the genetic code of the SARS-CoV-2 to other viruses found in animals showed that it is incredibly similar to other types of coronaviruses found in bats, leading the scientists to speculate that bats are the natural hosts of this virus [1]. Interestingly, a dive into the viral origins of other serious infectious diseases, such as SARS, rabies, and Ebola, shows that bats are also the probable hosts and “reservoirs” of these viruses. So, why do bats seem to be at the source of many new viral outbreaks?

 

What makes bats good viral hosts?

Bats are one of the largest and most diverse orders of animals on the planet. Their numerous species account for about 20% of all known mammalian species [2]. Though bats and humans infrequently interact due to bats’ nocturnal habits which contribute to their mysterious nature, what we know about bats proves that they are truly unique compared to other mammals. Most notably, bats are the only mammals capable of self-powered flight. Bats are also known for their use of echolocation, a technique involving producing sounds and listening to how the sounds echo from nearby objects, for navigation and capturing prey. Much less widely known, however, is that bats also have the capacity to carry a large number of different viruses while never dying from them or even showing any symptoms of infection.

While neuroscientists have studied bats to understand their various specialized skills (see these previous NeuWrite articles on bat skills here, here, and here), these private animals have often proved difficult to study in the laboratory and in the wild. Despite this, infectious disease scientists have spent many years trying to understand how bats’ unique physical and behavioral traits contribute to their ability to carry and spread viruses to animals and humans. The prevailing theories can be described by six factors:

1. Their relatively long lifespans. For most mammals, life expectancy is related to metabolic rate (the amount of energy an animal needs to live and perform tasks) and body size. A lower metabolic rate and larger body size is associated with a longer lifespan. This rule is followed, for example, by humans (large body, low energy needs, long lifespan) and mice (small bodies, high energy usage, relatively short lifespans). Bats, however, have small bodies and use huge amounts of energy to power their flight, yet many bat species exhibit lifespans that exceed 25-30 years [2]. Long periods of infectiousness over a long lifespan increases the chances for bats to transmit their viruses to other animals.

2. The timing of their evolution. Bats appeared early in the history of mammalian evolution. Scientists estimate that the most recent common ancestor for bats (the species that all of the current bat species evolved from) lived 64 million years ago [3]. Some of the common bat viruses also appear to have similarly ancient origins. These viruses may have been evolving for a long time to take advantage of how mammalian bodies function, changing their strategies of infection based on how the immune system works, the cell types that make up the mammalian body, and other factors. This would make it easier for them to spread to other mammals like humans [2].

3. Their living arrangements. Bats are miserable at “social distancing” and tend to live in very close quarters in high density populations. In the Southwestern United States, Mexican free-tail bats can roost in packs of up to 300 bats per square foot [2] and the Oklahoma Department of Wildlife Conservation estimates that up to 245,000 bats live in one of their more notorious caves [4]. As we have learned from social distancing measures, the proximity among people is an important factor in how easily a disease is able to spread. Additionally, bats don’t only stick with their own species. This propensity to live with other types of bats in dense living conditions is thought to greatly increase viral spread [5].

4. They hibernate. Many bat species, especially those that live in temperate climates, exhibit both seasonal hibernation and daily torpor, which is a period of inactivity. During hibernation, a bat’s body temperature can reach freezing and their body’s metabolic rate drops drastically. This is thought to suppress hibernating animals’ immune system, including a 90% decrease in the number of white blood cells, whose job it is to find and destroy pathogens, circulating throughout the body [6]. If a bat is infected with a virus during hibernation, it won’t begin to make antibodies against that specific virus until after it returns to a normal body temperature, allowing viruses to continue to make more viral particles during hibernation and torpor [2].

5. The way their immune system works. The most obvious place to look to determine how bats can harbor and spread viruses is their immune system. First, studies of white blood cells in normally active bats show that the types and ratios of these cells in bat tissue are not all that different from in other mammals, including humans. It appears that bats may, however, have a slightly larger number of white blood cells circulating in their bodies [7,8].

Bats and other mammals share aspects of their immune systems related to how cells recognize invaders and coordinate a response against them. Despite this similarity, a major difference in this “innate” immunity is clear when studying interferons, which are molecules that communicate to nearby cells to increase their antiviral defenses, thus preventing viruses from spreading from cell to cell. Whereas humans and other mammals have only a few different types of interferons, bats exhibit up to 12 different types of these signalling molecules [7]. Also, importantly, the interferon system, which is mostly shut down in the absence of a threat in other mammals, is always on in bat cells, meaning that bat cells can begin their response against a virus immediately. Viruses that make it through this defense can mutate to produce viruses that ignore interferon signalling in other mammals [9].

This fact, and the finding that some bats have a decreased duration and magnitude of other immunological response (like making antibodies against a virus) as compared to rabbits and guinea pigs, indicates that bats have sophisticated differences in their immune systems that could provide them with the ability to carry and spread a viral load without dying from it [7].

6. Their ability to fly. Bats are the only mammals capable of self-powered flight, which requires up to 5 times the energy usage capabilities of maximum exercise for other mammals. There are a variety of theories suggesting that flying-related factors also select for the ability to asymptomatically carry viruses. First, the high energy usage for flight can cause a build up of harmful, DNA-damaging molecules, which is believed to have led to an evolutionary change in bats’ genetic code that enhances genes related to the protection against and repair of DNA damage. Interestingly, these same genes also may play a role in the bat immune system, which may allow bats to maintain viral infections [10,11].

Also, flight causes a large increase in body temperature that is a bit like other mammals’ fever response to a virus. A major symptom of COVID-19 is a fever, which occurs when the body increases its core temperature to support an immune system response and to reach a temperature which will kill the virus. It is hypothesized that the increased body temperature bats achieve during flight protects against early attempts of the virus to take hold and cause symptoms. Furthermore, because bats experience huge variations in body temperature each day as they cycle through periods of torpor and flight, it is thought that viruses may mutate to be able to withstand these temperatures and therefore a human fever [12].

 

 

What are we doing about bat-borne diseases?

    The list of viruses that bats carry, many of which have made the jump to humans, is truly extensive. The most relevant viruses include: coronaviruses (like SARS-CoV which is the causative agent for severe acute respiratory syndrome SARS, and our current SARS-CoV-2 which causes COVID-19), Ebola virus, Dengue virus, Japanese encephalitis virus, West Nile virus, Yellow fever virus, Hendra virus, Nipah virus, Rabies virus, and European and Australian bat lyssavirus [13].

Due to these major public health concerns, certain procedures have been put into effect in high-risk areas to address bat-borne zoonotic disease spread. For example, a Malaysian outbreak of Nipah virus originating in pig farms caused officials to urge penning of pigs in structures with screened-in sides and the avoidance of growing desirable fruits near animal farms to avoid attracting fruit bats carrying the virus [14]. Vaccine programs for pre- and post-exposure use in humans have been successful for some of these viruses, such as rabies virus and bat lyssavirus. Also, vaccines have been developed for use in wildlife themselves, by hiding the components of a vaccine in food baits. It is thought that this strategy could be modified to immunize bats themselves against the deadly viruses they can harbor [14].

 

Do we really need bats?

 

As human actions, such as deforestation and consumption of wild meats from live animal markets, continue to increase the opportunities for transmission of bat viruses to human and domesticated animal populations, it would be easy for us to consider a life without bats to decrease the risks to public health. It must be noted, however, that bats constitute an irreplaceable part of our worldwide ecosystems. A 2011 study suggests that losing bats in North America would amount to $3.7 billion per year in agricultural losses, as bats are responsible for eating a majority of the nocturnal insects that destroy crops [15]. We also use bats as important models for communication, due to their use of echolocation, and flight technology, due to their agility in the skies [16].

As we continue to figure out life in the wake of the global COVID-19 pandemic, it will be important to consider how our own relationship with our global environment and species of all types has an impact on our public health.

 

 

 

References

1. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF (2020) The proximal origin of SARS-CoV-2. Nature Medicine, https://doi.org/10.1038/s41591-020-0820-9
2. Calisher CH, Childs JE, Field HE, Holmes KV, Schountz T (2006) Bats: important reservoir hosts of emerging viruses. Clinical Microbiology Reviews, 19(3):531-545
3. Teeling EC, Springer MS, Madsen O, Bates P, O’Brien SJ, Murphy WJ (2005) A molecular phylogeny for bats illuminates biogeography and the fossil record. Science, 307:580-584
4. Caire W, Matlack RS, Canow KB. Population size estimations of mexican free-tailed bat, Tadaria brasiliensis, at important maternity roosts in Oklahoma. Final performance report for grant number: F10AF00235 (T-55-R-1) by State Wildlife Grants. Grant period: Aug 2010-July 2013
5. Luis AD, Hayman DTS, O’Shea TJ, Cryan PM, Gilbert AT, Pulliam JRC, Mills JN, Timonin ME, Willis CKR, Cunningham AA, Fooks AR, Rupprecht CE, Wood JLN, Webb CT (2013) A comparison of bats and rodents as reservoirs of zoonotic viruses: are bats special? Proceedings of the Royal Society B, 280:20122753
6. Bouma HR, Carey HV, Kroese FGM (2010) Hibernation: the immune system at rest? Journal of Leukocyte Biology, 88:619-624
7. Baker ML, Schountz T, Wang LF (2013) Antiviral immune responses of bats: a review. Zoonoses and Public Health, 60:104-116
8. Turmelle AS, Ellison JA, Mendonca MT, McCracken GF (2010) Histological assessment of cellular immune response to the phytohemagglutinin skin test in Brazilian free-tailed bats (Tadarida brasiliensis). J Comp Physiol B, 180:1155-1164
9. Schountz T, Baker ML, Butler J, Munster V (2017) Immunological control of viral infections in bats and the emergence of viruses highly pathogenic to humans. Frontiers in Immunology, 8:1098
10. Shen YY, Liang L, Zhu ZH, Zhou WP, Irwin DM, Zhang YP (2010) Adaptive evolution of energy metabolism genes and the origin of flight in bats. PNAS, 107(19):8666-8671
11. Zhang G, Cowled C, Shi Z, Huang Z, Bishop-Lilly KA, Fang X, Wynne JW, Xiong Z, Baker ML, Zhao W, Tachedjian M, Zhu Y, Zhou P, Jiang X, Ng J, Yang L, Wu L, Xiao J, Feng Y, Chen Y, Sun X, Zhang Y, Marsh GA, Crameri G, Broder CC, Frey KG, Wang LF, Wang J (2013) Comparative analysis of bat genomes provides insight into the evolution of flight and immunity. Science, 339:456-460
12. O’Shea TJ, Cryan PM, Cunningham AA, Fooks AR, Hayman DTS, Luis AD, Peel AJ, Plowright RK, Wood JLN (2014) Bat flight and zoonotic viruses, Emerging Infectious Disease (CDC), 20(5):741-745
13. Wong S, Lau S, Woo P, Yuen KY (2007) Bats as a continuing source of emerging infections in humans. Reviews in Medical Virology, 17:67-91
14. Mackenzie JS, Field HE, Guyatt KJ (2003) Managing emerging diseases borne by fruit bats (flying foxes), with particular reference to henipaviruses and Australian bat lyssavirus. Journal of Applied Microbiology, 94:59S-69S
15. Boyles JG, Cryan PM, McCracken GF, Kunz TH (2011) Economic impact of bats in agriculture. Science, 332:41-42
16. Whiteman L, Kunz T, Langwig K, Simmons J, Horowitz S, McCracken G, Foster J, Frick W, Kilpatrick AM (2012) The night life: why we need bats all the time – not just on Halloween. National Science Foundation, nsf.gov

Cover Image Source: Wikimedia Commons