Bat virome


The bat virome is the group of viruses associated with bats. Bats host a diverse array of viruses, including all seven types described by the Baltimore classification system: double-stranded DNA viruses; single-stranded DNA viruses; double-stranded RNA viruses; positive-sense RNA viruses; negative-sense RNA viruses; positive-sense RNA viruses that replicate through a DNA intermediate; and double-stranded DNA viruses that replicate through a single-stranded RNA intermediate. The greatest share of bat-associated viruses identified as of 2020 are of type IV, in the family Coronaviridae.
Bats harbor many viruses and a few of them are zoonotic, or capable of infecting humans and causing disease, thus, are considered important emerging viruses. These zoonotic viruses include the rabies virus, SARS-CoV, MERS-CoV, Marburg virus, Nipah virus, and Hendra virus. While research strongly indicates that SARS-CoV-2 originated in bats, it is unknown how it was transmitted to humans, or if an intermediate host was involved. It has been speculated that bats may have a role in the ecology of Ebola virus, though this is unconfirmed. A closely-related ebolavirus, Bombali ebolavirus, has been detected in insectivorous bats. While transmission of rabies from bats to humans usually occurs from bites or scratches, most other zoonotic bat viruses are transmitted by direct contact with infected bat fluids like urine, guano, or saliva, or through contact with an infected, non-bat intermediate host. There is no firm evidence that butchering or consuming bat meat can lead to viral transmission, though this has been speculated because such activity causes aerosols that may facilitate respiratory transmission.
Despite the abundance of viruses associated with bats, they rarely become ill from viral infections, and rabies and Tacaribe viruses are the only viruses known to kill bats. A limited amount of research has been conducted on bat virology, particularly bat immune response. Bat immune systems are mostly similar to other mammals; however they differ in their lack of several inflammasomes, which activate the body's inflammatory response, as well as a dampened stimulator of interferon genes response, which helps control host response to pathogens. Some research indicates that bats have limited affinity maturation in their antibody responses to infection, whereas others show they make high-titer and durable antibody responses. Collectively, studies suggest that bats may be more tolerant of viruses than other mammals, although the basis of this tolerance is unknown. Suppression of bat immune responses can lead to disease from viral infection, suggesting that immune tolerance is not a mechanism of tolerance to viruses.
While much research has centered on bats as a source of zoonotic viruses, reviews have found mixed results on whether bats harbor more zoonotic viruses than other groups. A 2015 review found that bats do not harbor more zoonotic viruses than primates or rodents, though the three groups harbored more than other mammal orders. In contrast, a 2020 review found that bats do not have more zoonotic viruses than any other bird or mammal group when viral diversity is measured relative to host diversity, as bats are the second-most diverse order of mammals.

Viral diversity

Viruses have been found in bat populations around the world. Bats harbor all groups of viruses in the Baltimore classification, representing at least 28 families of viruses. Most of the viruses harbored by bats are RNA viruses, though they are also known to have DNA viruses. Bats are more tolerant of viruses than terrestrial mammals. A single bat can host several different kinds of viruses without becoming ill. Bats have also been shown to be more susceptible to reinfection with the same viruses, whereas other mammals, especially humans, have a greater propensity for developing varying degrees of immunity. Their behavior and life history also make them "exquisitely suitable hosts of viruses and other disease agents", with long lifespans, the ability to enter torpor or hibernate, and their ability to traverse landscapes with daily and seasonal movement.
Though bats harbor diverse viruses, they are rarely lethal to the bat host. Various factors have been implicated in bats' ability to survive viral infections. One suggestion is bats' use of flight. Some have proposed that flight produces a fever-like response, resulting in elevated temperature and metabolic rate. Additionally, this fever-like hypothesis may help them cope with actual fevers upon getting a viral infection. But there is no experimental evidence that suggests "flight as fever" is real. The fever response is much more sophisticated than just elevated body temperature, and includes production of a number of immune mediators, including prostaglandins and interleukin-1. A study that compared virus replication in bat cells incubated at elevated temperatures showed no difference in replication, which argues agains "flight as fever" hypothesis.
Some research indicates that bats' immune systems have allowed them to cope with a variety of viruses. A 2018 study found that bats have a dampened STING response compared to other mammals, which could allow them to respond to viral threats without over-responding. STING is a signaling molecule that helps coordinate various host defense genes against pathogens. The authors of the study concluded that "the weakened, but not entirely lost, functionality of STING may have profound impact for bats to maintain the balanced state of 'effective response' but not 'over response' against viruses."
Additionally, bats lack several inflammasomes found in other mammals; other inflammasomes are present with a greatly reduced response. While inflammation is an immune response to viruses, excessive inflammation is damaging to the body, and viruses like severe acute respiratory syndrome coronavirus are known to kill humans by inducing excessive inflammation. Bats' immune systems may have evolved to be more tolerant of stressors such as viral infections compared to other mammals.

Transmission to humans

The vast majority of bat viruses have no zoonotic potential, meaning they cannot be transmitted to humans. The zoonotic viruses have four possible routes of transmission to humans: contact with bat body fluids ; intermediate hosts; environmental exposure; and blood-feeding arthropods. Lyssaviruses like the rabies virus are transmitted from bats to humans via biting. Transmission of most other viruses does not appear to take place via biting, however. Contact with bat fluids such as guano, urine, and saliva is an important source of spillover from bats to humans. Other mammals may play a role in transmitting bat viruses to people, with pig farms a source of bat-borne viruses in Malaysia and Australia. Other possible transmission routes of bat-borne viruses are more speculative. It is possible but unconfirmed that hunting, butchering, and consuming bat meat can result in viral spillover. While arthropods like mosquitoes, ticks, and fleas may transmit viral infections from other mammals to humans, it is highly speculative that arthropods play a role in mediating bat viruses to humans. There is little evidence of environmental transmission of viruses from bats to humans, meaning that bat-borne virus do not persist in the environment for long. However, a limited number of studies have been conducted on the subject.

Bats compared to other viral reservoirs

Bats and their viruses may be the subject of more research than viruses found in other mammal orders, an example of research bias. A 2015 review found that from 1999 to 2013, there were 300-1200 papers published about bat viruses annually, compared to 12-45 publications for marsupial viruses and only 1-9 studies for sloth viruses. The same review found that bats do not have significantly greater viral diversity than other mammal groups. Bats, rodents, and primates all harbored significantly more zoonotic viruses than other mammal groups, though the differences among the aforementioned three groups were not significant. A 2020 review of mammals and birds found that the identity of the taxonomic groups did not have any impact on the probability of harboring zoonotic viruses. Instead, more diverse groups had greater viral diversity. Bat life history traits and immunity, while likely influential in determining bat viral communities, were not associated with a greater probability of viral spillover into humans.

Sampling

Bats are sampled for viruses in a variety of ways. They can be tested for seropositivity for a given virus using a method like ELISA, which determines whether or not they have the corresponding antibodies for the virus. They can also be surveyed using molecular detection techniques like PCR, which can be used to replicate and amplify viral sequences. Histopathology, which is the microscopic examination of tissue, can also be used. Viruses have been isolated from bat blood, saliva, feces, tissue, and urine. Some sampling is non-invasive and does not require killing the bat for sampling, whereas other sampling requires sacrificing the animal first. A 2016 review found no significant difference in total number of viruses found and new viruses discovered between lethal and non-lethal studies. Several species of threatened bat have been killed for viral sampling, including the Comoro rousette, Hildegarde's tomb bat, Natal free-tailed bat, and the long-fingered bat.

Double-stranded DNA viruses

Adenoviruses

es have been detected in bat guano, urine, and oral and rectal swabs. They have been found in both megabats and microbats across a large geographic area. Bat adenoviruses are closely related to those finds in canids. The greatest diversity of bat adenoviruses has been found in Eurasia, though the virus family may be undersampled in bats overall.