The bat-virus relationship examined

While bats are found in abundance in most parts of the world, particularly in tropical and temperate climates, they rarely cause problems to human beings. However, over the past several years, bats have emerged as potential vectors of several viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the ongoing coronavirus disease 2019 (COVID-19) pandemic.

A new iScience journal tudy examines the role of bats as reservoirs of several viruses and the factors that contribute to the emergence of these viruses.

Study: Molecular, Ecological, And Behavioural Drivers of The Bat-Virus Relationship. Image Credit: Bernd Wolter / Shutterstock.com

Introduction

Of the over 1,400 bat species of the order Chiroptera, all belong to one of two suborders, including Yinpterochiroptera and Yangochiroptera. Bats are considered keystone species, as they control the infestation of nocturnal insects and pests, thus benefiting agricultural practices and human health. Bats also help replant denuded forests, are major pollinators for many wild edible plants, and yield guano, a rich fertilizer.

Bats host many viruses, some of which have caused major zoonotic outbreaks of severe and sometimes fatal diseases. This may occur through direct transmission or secondary spread involving an intermediate animal host.

Some of the most notable viruses associated with bats include Ebola, Marburg, filovirus, Nipah, and Hendra viruses, as well as SARS-CoV, the Middle East respiratory syndrome (MERS) coronavirus (CoV), and SARS-CoV-2.

The porcine epidemic diarrhea virus (PEDV) and swine acute diarrhea syndrome coronavirus (SADS-CoV) may be tentatively added to this list. Interestingly, few bats appear to be sickened by these or other viruses, with the notable exception of rabies, Tacaribe, and rabies-related lyssaviruses.

Why bats are good reservoirs

Some features of bats that make them suitable as virus reservoirs include their ability to fly and cover long distances. During flight, bats achieve body temperatures that might inhibit viral replication, thus making these mammals relatively less vulnerable to infection while enhancing the immune response.

Bats also migrate seasonally, sometimes over hundreds of miles. This causes bats that are native to one place to become infected with new viruses from their migration home, especially because different bat species share the same roost. Moreover, migration could induce impaired immunity and thus allow chronic viral infections to reactivate.

Echolocation is another unique trait of bats and may cause aerosolization of oropharyngeal fluids, mucus, and saliva, thereby allowing for the spread of viruses present in the oral or respiratory cavities. However, this remains to be proven.

Hibernation is a physiological response to extremely cold weather, coupled with the reduced availability of food sources. This allows viruses to enter dormancy within the bat reservoir and subsequently reactivate once new bats are born and ready to be infected. This has been shown to occur with alphaCoVs in some bat species.

The daily period of torpor seen in most bats is another phenomenon that may favor the coexistence of viruses due to mutually beneficial adaptations in either species.

Longevity is significant for bats, as their lifespan can range from 20-40 years, depending on the species. While this is due to multiple factors, including their ability to take to the air to escape predators and their cooperative social behavior, along with some biological characteristics, longevity is also determined by genes which, in some cases, also favor virus tolerance.

The tendency of bats to roost in caves in large numbers, often from different species, encourages virus circulation and persistence, as well as virus jump across species barriers.

Since bats may not be able to eat much at a time due to the need to fly, they discard partly digested food on the ground that may contain potentially virus-contaminated saliva. This could lead to infection in other mammals foraging in the same area, as observed during Nipah or Hendra virus outbreaks in humans.

Nevertheless, zoonoses are not constantly being transmitted, and all bats are not infected, nor do all infected bats always shed the virus.

The immune system in Pterocarpus alectus bats appears to be adapted to infection with many viruses without developing lethal or severe disease.

Bats respond to viruses mostly through their innate immune system, which involves interferons (IFNs) that protect infected cells from further infection and prevent viral spread to neighboring cells. Moreover, IFN regulatory factor 7 (IRF7), which is important in the transcription of antiviral factors, is found in P. alectus as well, but not in other species.

Different bat species may have evolved alternative antiviral strategies, including a potential shift towards an IFNω driven response relative to IFNα in at least 10 bat species.”

Thus, bats exhibit significant differences in their innate immune response that prevents high viral loads.

Zoonotic viruses borne by bats induce immune dysregulation in humans, with a hyper-reactive inflammatory process that causes severe disease. However, in bats, several mechanisms prevent this, including inhibition of the pro-inflammatory NLRP3 domain and loss of PYHIN genes, which results in reduced transcription and activation of inflammasomes.

In vivo studies

Bats have been shown in vivo to escape clinical disease when infected with Ebola, Nipah, Marburg, or Hendra viruses, as well as MERS, SARS-CoV, and Dengue viruses. The potential role of hibernation in viral transmission, the ability to transmit the Japanese encephalitis virus to Culex mosquitoes without viremia, and limited inflammation following infection with the aforementioned viruses have all been demonstrated.

Spillover from bats to humans

A recent model suggests that several factors determine the spillover of viruses from bats to humans. These include the density and distribution of the virus and prevalence of the infection among bats, the likelihood of infection, which is driven by the number of successful protein-protein interactions between viral and host proteins, as well as bat immunity.

In Africa, bats have adapted to living near and within city limits. Thus, these bats often harbor several viral pathogens, which may lead to spillover events due to the crowding of both humans and bats, as well as the common practice of hunting and large bushmeat market in these areas. Moreover, in these situations, bat viruses may adapt more rapidly to humans or, in some cases, to an intermediate host, because of selection pressure.

This phenomenon has been observed with MERS-CoV, which is now widespread in dromedaries, as well as Nipah viruses, which have adapted to pigs. Such changes promote the re-emergence of these viruses in humans, depending on the rate of contact and density of human dwellings in the same locality.

Approximately 100 and 200 protein-protein interactions (PPIs) have been identified as essential for Nipah and Ebola virus replication within humans, respectively. Some examples of these PPIs include viral entry, co-adaptation of host factors for viral replication, inhibition of host antiviral systems, and viral release from the infected cell.

With SARS-CoV-2, the angiotensin-converting enzyme 2 (ACE2) receptor of the host cell and viral spike receptor binding domain (S-RBD) must interact to mediate viral entry into the host cell. This requires a change in the receptor from bat ACE2 to human ACE2.

Conclusions

More research is needed to determine the factors that promote virus infection, persistence, and shedding in bats, their adaptation to other hosts, and the effects of altered ecology on bat biology.

Perhaps bat-borne virus spillover events could be avoided by conserving bat habitats, as well as avoiding stress and human encroachment or interference with bats. This might require the use of molecular studies, as bat breeding in laboratory settings is notoriously unsuccessful, and bats require exacting conditions to live as in the wild.

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.