Physiology and Immunology of Bats – A Special Reservoir of Deadly Viruses

The Dreadful Myth of Bram Stoker’s ‘Dracula Transforming into a Bat’ seems to be a Reality when Considering the Physiology and Immunology of Bats – A Special Reservoir of Deadly Viruses

Student contributors (Authors): Ms. Animikha Ghosh, Ms. Shrestha Sengupta, Students of B.Tech Biotechnology, Semester-IV, Department of Biotechnology

The vampire fear and the prevailing superstitions in societies:

It’s been one hundred and twenty-three years passed after its publication, the Gothic vampire tale; ‘Dracula’, written by the Irish author Abraham (“Bram”) Stoker is still staggeringly popular worldwide among all age groups and professions. The careful and detailed creations of horror-plots of the original story have terrified the readers and elicited nightmares from the 19^th century till today. The radical transformation of ‘Dracula’ into a bat, as depicted by Stoker, contributes a lot to the thrill of the story but unfortunately, it has also strengthened some of the prevailing superstitions, misinformation and credulous beliefs of the human minds about the bats – such as bats as ‘blood-sucking evil creatures’ or ‘symbols of devilish activities’. Some oriental and occidental societies still believe that bats drink human blood.

Bats are largely insectivorous and frugivores though some drink mammalian blood too:

Bats belong to the order Chiroptera, which is the second-largest species-rich mammalian order with over 1300 species that are distributed in every other continent except Antarctica (bats comprise >20% of the classified mammalian species on earth). The order Chiroptera has two sub-orders, Yinpterochiroptera (comprises both families of megabats and microbats) and Yangochiroptera (the remaining microbat families). Bats of these suborders have diverse food habits but a majority of the members of the microbat families are insectivorous, i.e. they feed on moths, mosquitoes, beetles, etc. The consumption of insects can be as high as more than 500 small-sized insects per hour for the single little brown bats. The bulk of the megabats and other microbats however are fruit-eaters or frugivores – eating fruits (bananas, mangoes, figs, and dates), seeds, and pollen from the flowers. Also, some bats feed on birds, frogs, lizards, and other bats, and very few even drink the blood of other mammals. This last group of bats, popularly known as ‘Vampire Bats’, belong to the subfamily Desmodontinae and are native to the Americas, ranging from Central to South America. They represent only three species (Desmodus rotundus, Diphylla ecaudata, and Diaemus youngi) among the 1300 bat species found globally. The commonly seen vampire bat or Desmodus rotundus solely take blood as their food, albeit it’s not the human blood but they feed on the blood of cows, sheep, and horses. Therefore, the prevailing concepts about bats as a human bloodsucker and this is a ‘morph of Vampire’ are biologically invalid.

Bats harbor diverse viruses and high-profile zoonotic viruses – A serious threat to public health:

Before going any further, it is necessary to define what a zoonotic virus is. According to the World Health Organization (WHO), any disease or infection that can be naturally transmitted from a vertebrate animal host (fishes, amphibians, reptiles, birds, and mammals) to humans is defined as a zoonotic disease, and therefore, any viral pathogen that causes a zoonotic disease is called a zoonotic virus. The novel coronavirus, SARS-CoV-2, causing the current COVID-19 pandemic is an example of a zoonotic virus that probably comes from particular species of bats to humans via a second animal host (probably the pangolin). Bats harbor a huge number of zoonotic viruses with the highest number of viruses found to be hosted per bat species among the mammal orders. Estimations have also revealed that there are about 9.8% of the bat species that act as the zoonotic hosts of these viruses (members of more than 15 families of viruses) to cause >25 unique zoonotic diseases. Virological, epidemiological and molecular studies have clearly established the links between the bat species as natural reservoirs of high-profile zoonotic viruses and the emergence and re-emergence of viral epidemics and pandemics in human populations – they include the fatal diseases caused by rabies (transmitted by the vampire bats through carnivores to humans) and other related lyssa viruses, Nipah virus infection with fatal encephalitis (case fatality rate >70%) and diseases caused by other Henipaviruses such as Hendra viruses, Marburg virus disease with hemorrhagic fever (case fatality rate is between 25% and 100%), Ebola haemorrhagic fever (case fatality rate is between 25% and 90%), and the coronaviruses causing acute respiratory syndromes such as the novel SARS (Severe Acute Respiratory Syndrome) coronavirus (case fatality rate of 10%), the novel MERS (Middle East respiratory syndrome) coronavirus (case fatality rate of 34.4%) and the novel SARS-CoV-2 (case fatality rate of 6.2% till 29.05.2020) that is causing the current COVID-19 pandemic.

Apart from the highly pathogenic viruses, the huge viral diversity found in bat species also includes viruses which are not yet reported to be transmitted from bats to other animal hosts or causing human diseases, and even for some of them, it is still unclear whether bats are one of their important natural reservoirs such as particular alphaviruses, flaviviruses, and bunyaviruses.

Bats are special reservoir hosts of viruses owing to their unique physiology and immunology – The current status of knowledge:

Bats are the reservoir hosts of a plethora of zoonotic viruses partly because of the lifestyles of the different species to live together in overlapping geographic regions at the same time (a phenomenon called sympatry) which results in increased sharing of viruses between the species due to profound inter-species transmission. Though bats act as the natural reservoirs of viruses that are virulent for other animals and humans, rarely bats die or show clinical symptoms of these viral diseases. The maintenance of high viral diversity with low virulence in bats has led to many speculative hypotheses on the functional mechanisms that bats use to regulate viral replications more efficiently compared to other mammals. One such hypothesis states that evolution of flight is associated with high viral-tolerance in bats as the increased metabolic rate and the higher body temperature of bats during the flight together probably played the role of a general immune booster on an evolutionary timescale to select for the mitigating of virulence of the infecting-viruses at the cost of fostering viral diversity in the bat populations. This eventually enables bats to tolerate a greater diversity of virulent viruses by metabolic and thermal activations of the different branches of the immune system, such as the components of the innate and adaptive immune systems. Support for this hypothesis came from the following evidences – substantial increase in the rate metabolism (15-17 fold) in bats during flight compared to the resting state and this increase is way higher than the increase in metabolic rates of a flying bird (2 fold) or a sprinting rodent (7 fold), laboratory strains of mice inbred for higher metabolic rates surmount significantly stronger and specific immune responses compared to the mice bred for lower metabolic rates when challenged with a specific antigen,  evolution of flight behavior in bats was accompanied by genetic changes linked with the crucial requirement of repairing DNA damages due to increased rate of metabolism, elevation of core body temperature, typically found during mammalian fever (38^oC – 41^oC), in different bat species during their flights (e.g. Rousettus aegyptiacus: 38.2^oC – 41.2^oC, Eptisicus fuscus: 41^oC, Eumops perotis: 37.8^oC – 39.3^oC, Carollia perspicillata: 40.2^oC), and lastly the possible anti-viral innate and adaptive immune responses that can be induced in bats by high body temperature (enhancement in leukocyte mobility and interferon production, increased antibody production and cytokine responses, and increased T-helper cell responses etc.). These results, in lights of the physiology and immune system of bats and viral diversity, strongly suggest that bats are special reservoir hosts of zoonotic viruses owing to their flight behavior that escalates the immune responses on a daily-basis to possibly promote a form of evolution in the bat-borne viruses which enable them to sustain infections in bats without causing the diseases.

More direct evidence has disclosed two unique anti-viral mechanisms operating in the bats which are never reported previously in any other model system; these are respectively the chronic but regulated inflammatory responses and the antibody-level independent protective immunity. The innate immune system of bats responds to viral infections through type-I interferon (IFN) and the IFN-stimulated genes or ISGs, which eventually leads to the expressions of antiviral and pro-inflammatory cytokines. However, unlike humans, bats can regulate the high-levels of virus-induced pro-inflammatory responses, and thereby limit the tissue damage, by novel mechanisms (one of them is repressing the expressions of cytokine genes) but at the same time preserving the IFN-responses persistently to check viral replication. Interestingly, though bats have all the major subclasses of antibody (IgA, IgG, IgM, and IgE), under conditions of a challenge with the viral antigens, they expressed low titers of antibodies, even sometimes below the threshold of seropositivity, although the animals became seronegative at that time with no detectable viremia or viral shedding. The antibodies isolated from the bats, after they became seronegative, also didn’t show any neutralizing reaction to the antigens. This peculiar behavior of bat antibodies, of not showing viral neutralization, together with the persistent pro-inflammatory responses and the presence of a higher number of germline genes for antibodies than the humans confirm that the immune systems of bats are highly adapted to withstand the chronic load of diverse viruses, including the highly virulent ones, and possibly have substantial functional differences than that of the humans.

Our responsibilities to avoid further infections from the bats:

It is logical to state that virulent viruses although don’t make the bats sick but when transmitted (zoonotic events) from the bats to other animals, especially to human, whose immune pathways are unprepared to cope up with these viruses, can cause fatal diseases. The deadly epidemics and pandemics in humans, such as Ebola, SARS, MERS, Nipah, and the current COVID-19 are some of the blatant examples of human disasters in which bats played the villains by transmitting these viruses. However, accusing bats is nonsensical and is merely a way to escape our misdemeanor of interfering with the bats that have nucleated these catastrophes. Thus, we have to take vital responsibilities at this hour of crisis to avoid further bat-borne epidemics or pandemics, which include (by the WHO-guidelines) avoidance of contacts with the bats (bats are peri-domestic, so they often live in human residence), preserving their habitats, taking measures to check fruits for bat-inflicted perforations before selling them in the markets, planning agricultural land encroachment without destroying the forests, implementing re-forestations, and most importantly stop slaughtering bats for food. In the end, we have to remember that bats are neither our enemies nor vampires, but in reality, they are our true friends who are involved in maintaining the balance of our ecosystem and pollinating important crops to sustain our lives.

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