Virus bats

Ebola virus-specific immunoglobulin M antibody was detected in bats of the same species, but Ebola virus RNA was not detected in bats with antibody, and antibody was not detected in bats with Ebola virus RNA. Detection of Ebola virus RNA in bats and rodents is a fascinating finding, as is detection of antibody.

However, until and unless an Ebola virus or Marburg virus is isolated from a wild vertebrate, and experimental infections unambiguously demonstrate that the virus not only persists but is shed by that animal and that disease can be transmitted under controlled conditions, these findings will remain simply intriguing and promising.

Monath has postulated that there may be an as-yet-undetected Ebola virus, one that is nonpathogenic but may give rise to pathogenic genotypes by mutation, and that the filoviruses may be arthropod or plant viruses Scores of newly recognized viruses have emerged in recent decades, and elegant reviews have brought into focus the continuing importance of this phenomenon It seems surprising, as though we are caught unawares, when a hitherto unrecognized disease and its causative virus are discovered.

Recognition of the spillover of a zoonotic virus is precipitated by human, livestock, or wildlife deaths, with considerable medical, emotional, and economic miseries. When new emerging zoonotic viral diseases appear, reviews and grant applications are written, explanations proffered, symposia organized, and molecular and other specific diagnostic tools developed.

Unfortunately, one important method to predict emergence of zoonotic diseases that has been overlooked repeatedly is the natural history survey, followed by targeted studies of species of interest identified through the survey. Survey research followed by targeted study has been used successfully to explore the epidemiology of reservoir host-zoonotic virus maintenance, as exemplified by studies on hantaviruses in the southwestern United States , These studies have helped epidemiologists and public health officials make recommendations to reduce the risk of infection and to help forecast the location and severity of future outbreaks of hantavirus pulmonary syndrome 22 , 51 , 52 , From about to about , governments and private institutions emphasized sending people into the field to count, trap, measure, bleed, and test vertebrates and invertebrates for viruses.

Although those surveys may not have provided answers directly and quickly, they did provide specimens for future analyses and questions to be addressed. This invaluable but badly outdated compendium is slowly being replaced by Internet resources as a means of information dissemination. Supplementing and replacing this printed catalogue are numerous databases e. Nevertheless, most of the current data are limited in scope and in imagination.

What is needed is a survey of viruses of all vertebrates, invertebrates, plants, and other life forms. Although thoughts of complete surveys obviously are wishful thinking, some survey efforts are better than none. Information about the natural history of most viruses in bats is limited. Regarding the conservation status of bat species listed by Wilson , omitting those that are, or are suspected to be, extinct, Of the species that have not been assessed adequately, 38 9.

These 38 represent To various degrees, this can be said about all bats, if not about all vertebrates. Obviously, there is a need for comprehensive surveys of bats in every place where they occur, although conservation concerns must be addressed in the design of survey and sampling methods, given that bats of many species are protected.

Nonkilling techniques involving bleeding or procuring of oropharyngeal and rectal swabs for PCR-based analyses, in addition to collection of recently dead individuals, have been used to determine viral infections and the prevalence of antibodies in bats see, e. We know very little about the bat species that have been recognized, placed in a taxon, and largely ignored after that. How many unrecognized viruses do those bats harbor? Will any or all of these viruses eventually be shown to be human, livestock, or wildlife pathogens?

What new viruses lurk in the other nearly 4, species of mammals and the thousands of species of other vertebrates, invertebrates, plants, and individuals of other kingdoms, phyla, and classes? In effect, without even partial predictive capacity, we are simply waiting for the next disastrous zoonotic virus outbreak to occur. Clearly, this is not an effective prevention or prediction philosophy. However, there is no simple solution to this need. Perhaps part of the problem is lack of interest ignorance?

Surely in some countries, principally those from which emerging disease are emerging, there is a lack of infrastructure, manpower, and even national will; these are political questions. We suggest holding international symposia emphasizing the importance of both natural history surveys and of knowledge as not only predictive tools but also disease-prevention tools. Further emphasis on greater prioritization of such studies might be shown to be very cost-effective in the long run. Virus isolation techniques and PCR assays now are extremely sensitive and rapid.

These methods could provide the opportunity to collect and store a massive amount of information to accompany bat sera and tissue specimens. This would provide us with at least some degree of intellectual preparedness and with reagents that could be used to develop rapid diagnostic assays for newly emerged viruses.

In addition, viral proteins antigens can be expressed and used for serodiagnostic tests. If possible, the infectious virus is isolated, antigens are prepared for diagnosis, and experimental infections are conducted to study pathogenesis. Emerging viral diseases often are misdiagnosed. Only after it was realized that an intensive JEV vaccination campaign was not diminishing transmission of this new disease were other approaches initiated; by then, valuable time and many lives had been lost.

That outbreak can serve as an example of our perpetual following of epidemic curves rather than predicting them, of our lack of early recognition of emerging diseases. However, to detect previously unrecognized viruses, new reagents and approaches must be developed or existing techniques applied. Among the new reagents, a variety of nested primers useful for exploratory PCR might be formulated based on knowledge of sequences of recognized viruses within the order Mononegavirales which includes Bornaviridae , Rhabdoviridae , Filoviridae , and Paramyxoviridae [ ].

In addition, bat family-specific or genus-specific conjugates could be produced and applied for use in immunofluorescence assays or in enzyme-linked immunosorbent assays to identify antibodies in sera or blood samples, or antigens in tissue samples. Classical methods including hemagglutination-inhibition tests, which are broadly cross-reactive, also could be developed using inactivated antigens prepared from various recognized viruses.

Virus isolation assays, while potentially quite hazardous, also can be applied if used with appropriate biocontainment. In this day of increasing emphasis on molecular genetic tools for detecting viral nucleic acids and for identifying nucleotide sequences rather than the viruses themselves, it is frequently overlooked that virus isolation provides us with a virus.

With the virus itself, many areas of research and development can be addressed, including development of diagnostics, of animal disease models, and of vaccines. Emphasis, sometimes complete emphasis, on nucleotide sequence characterization rather than virus characterization has led us down a primrose path at the expense of having real viruses with which to work.

To understand the innate and acquired immune responses of bats during acute and chronic virus infections, much additional research is needed. It will be necessary to develop bat cell culture-based assays and bat-specific reagents to examine lymphocyte proliferation, antibody and cytokine synthesis, cell-mediated immune responses, and a host of other immunologic functions in bats that are important reservoirs of emerging viruses.

A major challenge in studying T-cell responses in bats is the apparent lack of inbred strains of bats. Such animals are needed for long-term T-cell studies because of the requirement for matched major histocompatibility complex molecules on T cells and antigen-presenting cells.

Colonies of captive bats might carry zoonotic viruses that could be transmitted to humans, so research on the bats and their cells might require biological containment. In rodents, the growth factors required for in vitro expansion and maturation of bone marrow stem cells into competent antigen-presenting cells have been partially characterized, leading to development of cell culture assays for intermediate-term propagation of rodent T cells Similar strategies likely can be employed for propagation of T cells from bats of various species.

Molecular genetics should be useful for analyzing bat immune responses. Despite this limitation, it should be possible to develop assays for evaluating such responses in infected bats. Perhaps most tractable and meaningful for understanding these responses are analyses of cytokines and chemokines, especially in conjunction with cell culture assays.

Capture enzyme-linked immunosorbent assays and flow cytometry-based assays for a number of cytokines and chemokines from conventional species have permitted an elegant dissection of immune responses in humans and rodents. However, development of monoclonal antibody pairs for cytokine detection assays requires substantial funding and effort. More recent developments employing molecular approaches, such as real-time PCR, cDNA arrays, and RNase protection assays, have accelerated development assays for cytokine and chemokine gene expression.

These assays will require sequencing of bat orthologs, but considering that 11 assemblies of mammalian genomes are already available, it is likely that most genes from bats of most species could be cloned and sequenced using degenerate PCR primer sets, a strategy that has been used for other species Once the relevant gene sequences are known for bats of a given species, real-time PCR assays could be developed.

In conjunction with cell culture studies, it should be possible to characterize bat immune responses to challenge with viral antigens.

These resources may be particularly valuable for rapidly identifying immune response or cytokine genes of interest by using human or mouse hybridization probes.

Viruses must evade the host immune response for a time sufficient to allow transmission to other susceptible hosts or to establish persistent infection. The strategies employed by viruses are numerous and target both the innate and adaptive phases of the immune response. Some commonly employed evasion strategies include virus-encoded immune-modulating cytokines, decoy soluble cytokine receptors, inhibitors of apoptosis and cellular signaling, inhibitors of antigen processing, and T-cell antagonists 2 , 3 , 18 , 61 , 70 , 79 , 87 , , , To persist, viruses must also become biochemically adapted, so that they can replicate without severely compromising the host's survival.

Some viruses, including SARS-CoV, elicit an immune response in the nonreservoir host that may contribute to pathology 75 , , while apparently, at least for SARS viruses, not causing immunopathology in the reservoir. Elucidating the immune responses in reservoir hosts that determine the balance between virus persistence and immunopathology could contribute to our understanding of viral pathogenesis in humans and reveal potential targets for therapeutic intervention.

How the viral proteins might affect potential interferon responses to virus infections in bats is unknown. Possibly the V proteins play a role in viral persistence and evasion of the immune response. Addressing these important issues regarding the pathophysiology of viral infections in bats will require the development of infection models for reservoir species of each zoonotic virus. In nonlethal rabies infections produced in Mexican free-tailed bats, individuals surviving infection do not have virus in the brain or saliva.

In one experimental study of free-tailed bats inoculated with salivary gland tissues from naturally infected bats, the incubation periods were 24 to days, but one asymptomatic bat sacrificed at the end of the study had rabies virus in the brain, salivary glands, and other organs Incubation periods for rabies virus are certainly highly variable in bats, and persistence of virus in hibernating bats has been suggested as serving a viral reservoir function A carrier state for rabies virus has also been suggested by experimental and observational studies among dogs in Ethiopia It is, perhaps, instructive that viruses of the families Paramyxoviridae , Filoviridae , Bornaviridae , and Rhabdoviridae are phylogenetically related and have been grouped in a single order, the Mononegavirales There are at least recognized viruses in this order, including some that infect humans, other primates, livestock, birds, dogs, seals, fish, crabs, mosquitoes, ticks, amoebae, plants, or bats.

If there is an unrecognized tendency for bats and viruses to be associated, viruses of this order would be prime targets for beginning the search. Essentially every living life form investigated has been shown to host viruses, and bats are no exception. However, it is reasonable to query the roles of viruses of bats. What role, for example, does a fruit-eating bat play in the life cycle of a human or livestock pathogen? If human and livestock infections from bats simply are host-switching phenomena, why have these viruses not been recognized previously, and why have they emerged now?

Are these events the results of ecologic alterations, such as impingement of human activities on heretofore virgin areas, consequences of global climate change, or the product of improved surveillance activities coincident with the technical advances in diagnostic capabilities required to identify heretofore undescribed zoonotic viruses?

Are viruses of bats symbionts, parasites, or commensals? Is pathogenicity for humans and livestock simply a freak occurrence? Perhaps these emerging bat viruses are naturally transmitted by arthropods or by other potential vectors that have not been examined. Surely a fatal infection in a host is not in the long-term best interest of the virus.

Might fruit-eating bats transmit viruses to or from plants? Are insectivorous bats intermediate hosts between insects and vertebrates or plants? Are fruiting events part of periodic amplification cycles of viruses from frugivorous bats to wildlife and humans, as suggested by Dobson 42?

Childs summarized the processes by which zoonotic viruses are transmitted He noted the rarity of surveillance for wildlife diseases or infections and suggested that such studies usually are outbreak-driven, i.

Are transmissions between bats and other vertebrates infrequent, incidental spillover events? Do bats differ from other mammals in their ability to clear viral infections? Does the persistence of asymptomatic viral infections in bats indicate that bats are an important reservoir for the wide variety of viruses in nature?

Is the prevalence of RNA viruses in persistent infections in bats indicative of a defect in host resistance or viral clearance mechanisms, such as interferon or interferon-responsive genes that lead to clearance of RNA viruses from other vertebrates? There is some urgency to explore these important questions. There is no reason to believe that bats are different from other mammals with regard to species specificity of host susceptibility to virus diseases, nonuniform persistence of viral infections, or mechanisms of virus shedding, so that such investigations likely do not require development of new assay systems or diagnostic concepts.

Additional research is needed to determine the roles played by bats of various species in the natural histories of the viruses for which bats can serve as hosts. As well, viruses have been isolated from bats not identified further than to genus level and from four unidentified bats. Some viruses have been isolated from bats of as few as 1 species and one from as many as Clearly, bat handlers, people entering bat habitat areas, and people who usually think in noninfectious disease terms regarding various studies of the bats themselves should take necessary precautions to avoid exposing themselves to recognized and unrecognized viruses and to other human pathogens which the bats may harbor.

In addition to finding a recent publication reporting the indentification of six novel coronaviruses from six different bat species in Hong Kong alone P. Woo, S. Lau, K. Li, R. Poon, B. Wong, H. Tsoi, B. Yip, Y. Huang, K. Chan, and K. Yuen, Virology, Epub ahead of print, doi Thus, our article may contain only an indication of the great potential for future discoveries of viruses in bats worldwide. Centers for Disease Control and Prevention, for providing insights and sharing with us his vast experiences with bats in Africa and North America.

Meredith Happold, Division of Botany and Zoology, Australian National University, Canberra, Australia, provided information unavailable to or overlooked by us as well as taxonomic advice and corrected errors in earlier versions of this paper. Finally, we thank the many people with whom we held constructive conversations and exchanges and who took time from their busy schedules to share with us their knowledge, counsel, fascinating experiences, and unpublished data. National Center for Biotechnology Information , U.

Journal List Clin Microbiol Rev v. Clin Microbiol Rev. Charles H. Childs , 2 Hume E. Field , 3 Kathryn V. Holmes , 4 and Tony Schountz 5. James E. Hume E. Kathryn V. Author information Copyright and License information Disclaimer. Phone: Fax: E-mail: ten. This article has been cited by other articles in PMC. TABLE 1. Species of bats order Chiroptera , by family and genus. Family and subfamily No. Open in a separate window.

TABLE 2. Viruses isolated from naturally-infected bats worldwide. Simmons and other sources. With few exceptions, e. Evolution and Phylogeny of Bats Whereas other mammals, such as certain species of rodents order Rodentia and carnivores order Carnivora , may possess traits in common with species of bats, such as the ability to hibernate, no group of mammals shares the full suite of attributes that make bats unique.

Ability To Fly Bats are unique among mammals in their ability to fly. Torpor and Hibernation An important trait of temperate bats of the families Vespertilionidae and Rhinolophidae is their ability to enter into daily torpor and seasonal hibernation to conserve energy during cool nights and winter months Long Life Span The extreme longevity of bats, together with the possibility that they might develop persistent infections with certain viruses, may help maintain the viruses and transmit them to other vertebrates.

Population Size and Roosting Behavior The frequently great population densities of bats and their crowded roosting behavior increase the likelihood of intra- and interspecies transmission of viral infections. Bat Population Structure The demographic and spatial structuring of bat populations is sufficiently variable to offer opportunities for viruses that cause both acute and persistent infections to be maintained.

Echolocation Microchiropteran bats are, with rare exceptions among the Megachiroptera 69 , 71 , the only land mammals that emit sounds and then detect and characterize the time delay and signal properties of returning echoes for the purpose of navigation echolocation.

Bat Immunology Why can certain viruses infect and persist in apparently healthy bats yet be highly pathogenic for humans and other vertebrates? Rabies Virus It would be impossible here to summarize the scientific literature with regard to rabies and rabies virus.

Lyssaviruses Related to Rabies Virus Rabies virus is related to other lyssaviruses from bats, rodents, and arthropods Henipaviruses In an outbreak of an acute respiratory illness occurred in a human and 14 horses in Hendra, a suburb of Brisbane, Australia.

Menangle and Tioman Viruses Menangle virus family Paramyxoviridae , genus Rubulavirus was isolated in from stillborn piglets at a large commercial piggery near Menangle in Australia ; the bat colony and the piggery had coexisted for 29 years before the incident.

Ebola Viruses Five viruses have been placed in the taxon Filoviridae. Studies on Immune Responses of Bats To understand the innate and acquired immune responses of bats during acute and chronic virus infections, much additional research is needed. Immune Evasion and Virus Persistence Viruses must evade the host immune response for a time sufficient to allow transmission to other susceptible hosts or to establish persistent infection.

Discovery of Emerging Viruses in Wildlife It is, perhaps, instructive that viruses of the families Paramyxoviridae , Filoviridae , Bornaviridae , and Rhabdoviridae are phylogenetically related and have been grouped in a single order, the Mononegavirales Aguilar-Setien, A. Loza-Rubio, M. Salas-Rojas, N. Brisseau, F.

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Person-to-person transmission of Nipah virus during outbreak in Faridpur District, February , posting date. Nipah virus—Bangladesh Tangail ProMED-mail archive no. Austad, S. Diverse aging rates in metazoans: targets for functional genomics. Ageing Dev. Badrane, H. Host switching in lyssavirus history from the Chiroptera to the Carnivora orders.

Baer, G. Experimental rabies infection in the Mexican freetail bat. Bat salivary gland virus carrier state in a naturally infected Mexican free-tail bat. Barbour, R. Bats of America. University Press of Kentucky, Lexington. Bell, G. A possible case of interspecific transmission of rabies in insectivorous bats. Bingham, J. Javangwe, C. Sabeta, A. Wandeler, and L. Report of isolations of unusual lyssaviruses rabies and Mokola virus identified retrospectively from Zimbabwe.

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Rota, P. Rollin, W. Bellini, T. Ksiazek, and A. Nipah virus-associated encephalitis outbreak, Siliguri, India. Chakravarty, A. Immunofluorescence analysis of immunoglobulin bearing lymphocytes in the Indian fruit bat: Pteropus giganteus. Lymphology 27 : Chant, K. Chan, M. Smith, D. Dwyer, and P. Probable human infection with a newly described virus in the family Paramyxoviridae.

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Tioman virus, a novel paramyxovirus isolated from fruit bats in Malaysia. Virology : Bellini, P. Rota, B. Harcourt, A. Tamin, S. Lam, T. Ksiazek, P. Rollin, S. Zaki, W. Goldsmith, D. Gubler, J. Roehrig, B. Eaton, A. Gould, J. Olson, H. Field, P. Daniels, A. Ling, C. Peters, L. Anderson, and B. Nipah virus: a recently emergent deadly paramyxovirus. Science : Koh, P.

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University of New Mexico Publications in Biology no. University of New Mexico Press, Albuquerque. Rabies transmission by air in bat caves , p. PHS publication no. Government Printing Office, Washington, D. Emmons, and J. Rabies virus in nasal mucosa of naturally infected bats. Daoust, P. Wandeler, and G. Cluster of rabies cases of probable bat origin among red foxes in Prince Edward Island, Canada. Davenport, B. Willis, J.

Prescott, R. Farrell, T. Coons, and T. Generation of competent bone marrow-derived antigen presenting cells from the deer mouse Peromyscus maniculatus. BMC Immunol. Dobson, A. One of the conspiracy theories that have plagued attempts to keep people informed during the pandemic is the idea that the coronavirus was created in a laboratory.

But the vast majority of scientists who have studied the virus agree that it evolved naturally and crossed into humans from an animal species, most likely a bat. The answers lie in the genetic material and evolutionary history of the virus, and understanding the ecology of the bats in question. SARS-CoV-2 is the newest of seven coronaviruses found in humans, all of which came from animals , either from bats, mice or domestic animals. Bats were also the source of the viruses causing Ebola, rabies, Nipah and Hendra virus infections, Marburg virus disease, and strains of Influenza A virus.

If the virus had been genetically engineered in a lab there would be signs of manipulation in the genome data. This would include evidence of an existing viral sequence as the backbone for the new virus, and obvious, targeted inserted or deleted genetic elements. But no such evidence exists. It is very unlikely that any techniques used to genetically engineer the virus would not leave a genetic signature , like specific identifiable pieces of DNA code.

The genome of SARS-CoV-2 is similar to that of other bat coronaviruses, as well as those of pangolins, all of which have a similar overall genomic architecture. Differences between the genomes of these coronaviruses show natural patterns typical of coronavirus evolution. More than 1, species of bats live around the world making up 20 percent of mammal species.

Probably not since humans are unlikely to come into contact with bats and none of the bat species in North America are known to have the virus that causes COVID What should I do if I see a bat?

If the bat is flying by in the evening, eating moths and other insects, enjoy watching it! But if you see a bat during the day, lying on the ground or roosting in a building, avoid touching the bat. It is important to never touch a bat, to protect the bat and you. Always call your Local Bat Experts for help. What is the National Park Service doing?

We continue our mission to protect and conserve bats. These incredible mammals already face serious challenges.