Filoviruses in Bats: Current Knowledge and Future Directions

Filoviruses, including Ebolavirus and Marburgvirus, pose significant threats to public health and species conservation by causing hemorrhagic fever outbreaks with high mortality rates. Since the first outbreak in 1967, their origins, natural history, and ecology remained elusive until recent studies linked them through molecular, serological, and virological studies to bats. We review the ecology, epidemiology, and natural history of these systems, drawing on examples from other bat-borne zoonoses, and highlight key areas for future research. We compare and contrast results from ecological and virological studies of bats and filoviruses with those of other systems. We also highlight how advanced methods, such as more recent serological assays, can be interlinked with flexible statistical methods and experimental studies to inform the field studies necessary to understand filovirus persistence in wildlife populations and cross-species transmission leading to outbreaks. We highlight the need for a more unified, global surveillance strategy for filoviruses in wildlife, and advocate for more integrated, multi-disciplinary approaches to understand dynamics in bat populations to ultimately mitigate or prevent potentially devastating disease outbreaks.

[1]  J. Wood,et al.  Ebola Virus Antibodies in Fruit Bats, Ghana, West Africa , 2012, Emerging infectious diseases.

[2]  W. Ian Lipkin,et al.  Discovery of an Ebolavirus-Like Filovirus in Europe , 2011, PLoS pathogens.

[3]  Yiming Bao,et al.  PAirwise Sequence Comparison (PASC) and Its Application in the Classification of Filoviruses , 2012, Viruses.

[4]  H. Feldmann,et al.  Classification, structure, and replication of filoviruses. , 1999, Current topics in microbiology and immunology.

[5]  Sebastian Funk,et al.  Using Mathematical Models In A UnifiedApproach To Predicting The Next EmergingInfectious Disease , 2012 .

[6]  L. Real,et al.  Correction for Wittmann et al., Isolates of Zaire ebolavirus from wild apes reveal genetic lineage and recombinants , 2007, Proceedings of the National Academy of Sciences.

[7]  Heinz Feldmann,et al.  Filoviridae: Marburg and ebola viruses , 2013 .

[8]  J. Epstein,et al.  Characterization of Nipah Virus from Naturally Infected Pteropus vampyrus Bats, Malaysia , 2010, Emerging infectious diseases.

[9]  A. Sanchez,et al.  Ebola (subtype Reston) virus among quarantined nonhuman primates recently imported from the Philippines to the United States. , 1999, The Journal of infectious diseases.

[10]  H. Karch,et al.  Non-O157:H7 pathogenic Shiga toxin-producing Escherichia coli: phenotypic and genetic profiling of virulence traits and evidence for clonality. , 1999, The Journal of infectious diseases.

[11]  Zhènglì Shí,et al.  Serological evidence of ebolavirus infection in bats, China , 2012, Virology Journal.

[12]  K. Dittmar,et al.  Evolutionary maintenance of filovirus-like genes in bat genomes , 2011, BMC Evolutionary Biology.

[13]  Jonathan Dushoff,et al.  Agricultural intensification, priming for persistence and the emergence of Nipah virus: a lethal bat-borne zoonosis , 2011, Journal of The Royal Society Interface.

[14]  H. Feldmann,et al.  Ebola haemorrhagic fever , 2011, The Lancet.

[15]  R. May,et al.  Population biology of infectious diseases: Part II , 1979, Nature.

[16]  J. Blanton,et al.  Trends in national surveillance data for bat rabies in the United States: 2001-2009. , 2012, Vector borne and zoonotic diseases.

[17]  T. Ksiazek,et al.  Chronological and spatial analysis of the 1996 Ebola Reston virus outbreak in a monkey breeding facility in the Philippines. , 2002, Experimental animals.

[18]  Alan Kemp,et al.  Isolation of Genetically Diverse Marburg Viruses from Egyptian Fruit Bats , 2009, PLoS pathogens.

[19]  W. Ian Lipkin,et al.  Newly Discovered Ebola Virus Associated with Hemorrhagic Fever Outbreak in Uganda , 2008, PLoS pathogens.

[20]  F. Bronson,et al.  Seasonal reproduction of a tropical bat, Anoura geoffroyi, in relation to photoperiod. , 1992, Journal of reproduction and fertility.

[21]  E. Gurley,et al.  Use of Infrared Camera to Understand Bats’ Access to Date Palm Sap: Implications for Preventing Nipah Virus Transmission , 2010, EcoHealth.

[22]  Lieping Chen,et al.  How Ebola and Marburg viruses battle the immune system , 2007, Nature Reviews Immunology.

[23]  N. Johnson,et al.  Bats and lyssaviruses. , 2011, Advances in virus research.

[24]  A. Sanchez,et al.  Epidemiology of Ebola (subtype Reston) virus in the Philippines, 1996. , 1999, The Journal of infectious diseases.

[25]  G. Kobinger,et al.  Replication, pathogenicity, shedding, and transmission of Zaire ebolavirus in pigs. , 2011, The Journal of infectious diseases.

[26]  C. D. de Jong,et al.  Sampling Small Quantities of Blood from Microbats , 2010 .

[27]  R. Salt,et al.  PERCUTANEOUS LUNG BIOPSY , 1976, The Lancet.

[28]  A. Peterson,et al.  Ecologic and Geographic Distribution of Filovirus Disease , 2004, Emerging infectious diseases.

[29]  G. Kobinger,et al.  Transmission of Ebola virus from pigs to non-human primates , 2012, Scientific Reports.

[30]  B. Finkenstädt,et al.  Statistical Inference in a Stochastic Epidemic SEIR Model with Control Intervention: Ebola as a Case Study , 2006, Biometrics.

[31]  C. Webb,et al.  A comparison of bats and rodents as reservoirs of zoonotic viruses: are bats special? , 2013, Proceedings of the Royal Society B: Biological Sciences.

[32]  P. Daniels,et al.  Transmission studies of Hendra virus (equine morbillivirus) in fruit bats, horses and cats. , 1998, Australian veterinary journal.

[33]  A. Peterson,et al.  Geographic potential for outbreaks of Marburg hemorrhagic fever. , 2006, The American journal of tropical medicine and hygiene.

[34]  A. Gorbalenya,et al.  Genetics-Based Classification of Filoviruses Calls for Expanded Sampling of Genomic Sequences , 2012, Viruses.

[35]  Peter D. Walsh,et al.  Ebola Outbreak Killed 5000 Gorillas , 2006, Science.

[36]  P. Jahrling,et al.  Ebola hemorrhagic fever: evaluation of passive immunotherapy in nonhuman primates. , 2007, The Journal of infectious diseases.

[37]  Jeremy Bruenn,et al.  Filoviruses are ancient and integrated into mammalian genomes , 2010, BMC Evolutionary Biology.

[38]  E. T. Hooper,et al.  Three Central American Bat Communitis: Structure, Reproductive Cycles, and Movement Patterns , 1972 .

[39]  G. Kobinger,et al.  Ebola and Marburg , 2009 .

[40]  C. Boesch,et al.  Histopathological and immunohistochemical studies of lesions associated with Ebola virus in a naturally infected chimpanzee. , 1999, The Journal of infectious diseases.

[41]  Bas Huijbregts,et al.  Catastrophic ape decline in western equatorial Africa , 2003, Nature.

[42]  Kevin J. Olival,et al.  Correlates of Viral Richness in Bats (Order Chiroptera) , 2009, EcoHealth.

[43]  R. DeSalle,et al.  Lack of population genetic structure and host specificity in the bat fly, Cyclopodia horsfieldi, across species of Pteropus bats in Southeast Asia , 2013, Parasites & Vectors.

[44]  C. Roth,et al.  Risk Factors for Marburg Hemorrhagic Fever, Democratic Republic of the Congo , 2003, Emerging infectious diseases.

[45]  P. Racey,et al.  Life-history and Reproductive Strategies of Bats , 2000 .

[46]  Timothy D. Flietstra,et al.  Seasonal Pulses of Marburg Virus Circulation in Juvenile Rousettus aegyptiacus Bats Coincide with Periods of Increased Risk of Human Infection , 2012, PLoS pathogens.

[47]  T. Ksiazek,et al.  Seroepidemiological study of filovirus related to Ebola in the Philippines , 1991, The Lancet.

[48]  L. H. Taylor,et al.  Identifying Reservoirs of Infection: A Conceptual and Practical Challenge , 2002, Emerging infectious diseases.

[49]  P. Jahrling,et al.  Characterization of a new Marburg virus isolated from a 1987 fatal case in Kenya. , 1996, Archives of virology. Supplementum.

[50]  S. Pattyn,et al.  Approaches towards studies on potential reservoirs of viral haemorrhagic fever in southern Sudan , 1978 .

[51]  A. McElroy,et al.  Development of a reverse genetics system to generate recombinant Marburg virus derived from a bat isolate. , 2013, Virology.

[52]  V. Sandig,et al.  Authentication of the R06E Fruit Bat Cell Line , 2012, Viruses.

[53]  A. Takada,et al.  Characterization of the Envelope Glycoprotein of a Novel Filovirus, Lloviu Virus , 2013, Journal of Virology.

[54]  R. Weiss,et al.  Virus neutralising activity of African fruit bat (Eidolon helvum) sera against emerging lyssaviruses , 2010, Virology.

[55]  Ghislain Moussavou,et al.  The natural history of Ebola virus in Africa. , 2005, Microbes and infection.

[56]  M. Müller,et al.  Amplification of Emerging Viruses in a Bat Colony , 2011, Emerging infectious diseases.

[57]  J. Epstein,et al.  Evidence for Nipah virus recrudescence and serological patterns of captive Pteropus vampyrus , 2011, Epidemiology and Infection.

[58]  J. Hyman,et al.  The basic reproductive number of Ebola and the effects of public health measures: the cases of Congo and Uganda. , 2004, Journal of theoretical biology.

[59]  M. V. Van Kerkhove,et al.  Marburg hemorrhagic fever in Durba and Watsa, Democratic Republic of the Congo: clinical documentation, features of illness, and treatment. , 2007, The Journal of infectious diseases.

[60]  C. Peters,et al.  Outbreak of fatal illness among captive macaques in the Philippines caused by an Ebola-related filovirus. , 1992, The American journal of tropical medicine and hygiene.

[61]  G. Gongal,et al.  A longitudinal study of the prevalence of Nipah virus in Pteropus lylei bats in Thailand: evidence for seasonal preference in disease transmission. , 2010, Vector borne and zoonotic diseases.

[62]  R. Plowright,et al.  The effect of seasonal birth pulses on pathogen persistence in wild mammal populations , 2014, Proceedings of the Royal Society B: Biological Sciences.

[63]  Kate E. Jones,et al.  A framework for the study of zoonotic disease emergence and its drivers: spillover of bat pathogens as a case study , 2012, Philosophical Transactions of the Royal Society B: Biological Sciences.

[64]  P. Formenty,et al.  Multiple Ebola Virus Transmission Events and Rapid Decline of Central African Wildlife , 2004, Science.

[65]  Donald W. Thomas The annual migrations of three species of West African fruit bats (Chiroptera: Pteropodidae) , 1983 .

[66]  C. Boesch,et al.  Ebola virus outbreak among wild chimpanzees living in a rain forest of Côte d'Ivoire. , 1999, The Journal of infectious diseases.

[67]  Foraging Behaviour and Landscape Utilisation by the Endangered Golden-Crowned Flying Fox (Acerodon jubatus), The Philippines , 2013, PloS one.

[68]  T. Mizutani,et al.  Reston Ebolavirus Antibodies in Bats, the Philippines , 2011, Emerging infectious diseases.

[69]  J. Rowcliffe,et al.  Demography of straw-colored fruit bats in Ghana , 2012, Journal of mammalogy.

[70]  H. Leirs,et al.  Search for the Ebola virus reservoir in Kikwit, Democratic Republic of the Congo: reflections on a vertebrate collection. , 1999, The Journal of infectious diseases.

[71]  Gerald S. Wilkinson,et al.  Birth synchrony in greater spear‐nosed bats (Phyllostomus hastatus) , 2001 .

[72]  C. Koh,et al.  Isolation of Nipah virus from Malaysian Island flying-foxes. , 2002, Microbes and infection.

[73]  A. Katzourakis,et al.  Endogenous Viral Elements in Animal Genomes , 2010, PLoS genetics.

[74]  K. Johnson,et al.  MARBURG-VIRUS DISEASE IN KENYA , 1982, The Lancet.

[75]  J. Wood,et al.  Long-Term Survival of an Urban Fruit Bat Seropositive for Ebola and Lagos Bat Viruses , 2010, PloS one.

[76]  J. Gonzalez,et al.  Large serological survey showing cocirculation of Ebola and Marburg viruses in Gabonese bat populations, and a high seroprevalence of both viruses in Rousettus aegyptiacus , 2009, BMC infectious diseases.

[77]  Stuart T. Nichol,et al.  Molecular Evolution of Viruses of the Family Filoviridae Based on 97 Whole-Genome Sequences , 2012, Journal of Virology.

[78]  S. Günther,et al.  Response to Imported Case of Marburg Hemorrhagic Fever, the Netherlands , 2009, Emerging infectious diseases.

[79]  Stephen P. Luby,et al.  A Strategy To Estimate Unknown Viral Diversity in Mammals , 2013, mBio.

[80]  R. Plowright,et al.  Urban habituation, ecological connectivity and epidemic dampening: the emergence of Hendra virus from flying foxes (Pteropus spp.) , 2011, Proceedings of the Royal Society B: Biological Sciences.

[81]  P. Jahrling,et al.  Experimental infection of cynomolgus macaques with Ebola-Reston filoviruses from the 1989-1990 U.S. epizootic. , 1996, Archives of virology. Supplementum.

[82]  Lijun Wu,et al.  Comparative Analysis of Bat Genomes Provides Insight into the Evolution of Flight and Immunity , 2013, Science.

[83]  J. Gonzalez,et al.  Spatial and temporal patterns of Zaire ebolavirus antibody prevalence in the possible reservoir bat species. , 2007, The Journal of infectious diseases.

[84]  R. Ostfeld,et al.  New Directions in Conservation Medicine Applied Cases of Ecological Health , 2012 .

[85]  D. Dimitrov,et al.  Neutralization assays for differential henipavirus serology using Bio-Plex protein array systems. , 2007, Journal of virological methods.

[86]  J. Epstein,et al.  The emergence of Nipah and Hendra virus: pathogen dynamics across a wildlife-livestock-human continuum. , 2006 .

[87]  M. Baker,et al.  Antiviral Immune Responses of Bats: A Review , 2012, Zoonoses and public health.

[88]  C. Broder,et al.  Viral antibody dynamics in a chiropteran host , 2013, The Journal of animal ecology.

[89]  A. Breed,et al.  Evidence of Henipavirus Infection in West African Fruit Bats , 2008, PloS one.

[90]  J. Childs,et al.  Trends in national surveillance for rabies among bats in the United States (1993-2000). , 2003, Journal of the American Veterinary Medical Association.

[91]  Jens H. Kuhn,et al.  Proposal for a revised taxonomy of the family Filoviridae: classification, names of taxa and viruses, and virus abbreviations , 2010, Archives of Virology.

[92]  T. Ksiazek,et al.  Experimental inoculation of plants and animals with Ebola virus. , 1996, Emerging infectious diseases.

[93]  A. Takada,et al.  Serological Evidence of Ebola Virus Infection in Indonesian Orangutans , 2012, PloS one.

[94]  J. Pawęska,et al.  Virological and Serological Findings in Rousettus aegyptiacus Experimentally Inoculated with Vero Cells-Adapted Hogan Strain of Marburg Virus , 2012, PloS one.

[95]  P. Formenty,et al.  Emergence of divergent Zaire ebola virus strains in Democratic Republic of the Congo in 2007 and 2008. , 2011, The Journal of infectious diseases.

[96]  R. Plowright,et al.  Deciphering Serology to Understand the Ecology of Infectious Diseases in Wildlife , 2013, EcoHealth.

[97]  R. May,et al.  Population Biology of Infectious Diseases , 1982, Dahlem Workshop Reports.

[98]  T. Breuer,et al.  Potential for Ebola Transmission between Gorilla and Chimpanzee Social Groups , 2007, The American Naturalist.

[99]  P. Jahrling,et al.  Preliminary report: isolation of Ebola virus from monkeys imported to USA , 1990, The Lancet.

[100]  D. Simpson,et al.  Fatal human disease from vervet monkeys. , 1967, Lancet.

[101]  A. Hyatt,et al.  Experimental Nipah virus infection in pigs and cats. , 2002, Journal of comparative pathology.

[102]  P. Sureau,et al.  Filoviridae: a taxonomic home for Marburg and Ebola viruses? , 1982, Intervirology.

[103]  Marburg haemorrhagic fever. , 2006, Nursing times.

[104]  Response to Imported Case of Marburg Hemorrhagic Fever, the Netherlands , 2009, Emerging Infectious Diseases.

[105]  J. Gonzalez,et al.  Ebolavirus and Other Filoviruses , 2007, Current topics in microbiology and immunology.

[106]  C. Webb,et al.  Ecology of Zoonotic Infectious Diseases in Bats: Current Knowledge and Future Directions , 2012, Zoonoses and public health.

[107]  Kevin J. Olival,et al.  Targeting Surveillance for Zoonotic Virus Discovery , 2013, Emerging infectious diseases.

[108]  H. Feldmann,et al.  Marburg and Ebola viruses. , 1996, Advances in virus research.

[109]  P. Formenty,et al.  Human Ebola outbreak resulting from direct exposure to fruit bats in Luebo, Democratic Republic of Congo, 2007. , 2009, Vector borne and zoonotic diseases.

[110]  P. Rollin,et al.  Genomic analysis of filoviruses associated with four viral hemorrhagic fever outbreaks in Uganda and the Democratic Republic of the Congo in 2012. , 2013, Virology.

[111]  P. Daszak,et al.  Henipavirus susceptibility to environmental variables. , 2008, Virus research.

[112]  M. T. McIntosh,et al.  Discovery of Swine as a Host for the Reston ebolavirus , 2009, Science.

[113]  Jens H. Kuhn,et al.  Virus nomenclature below the species level: a standardized nomenclature for filovirus strains and variants rescued from cDNA , 2013, Archives of Virology.

[114]  H. Zeller,et al.  [Democratic Republic of the Congo: between civil war and the Marburg virus. International Committee of Technical and Scientific Coordination of the Durba Epidemic]. , 1999, Medecine tropicale : revue du Corps de sante colonial.

[115]  Melissa M. Eitzen,et al.  Vaccines for Biodefense and Emerging and Neglected Diseases , 2009 .

[116]  C. Broder,et al.  Continent-wide panmixia of an African fruit bat facilitates transmission of potentially zoonotic viruses , 2013, Nature Communications.

[117]  A. Rowe,et al.  Clinical virology of Ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among EHF patients in Kikwit, Democratic Republic of the Congo, 1995. , 1999, The Journal of infectious diseases.

[118]  A. Barrett,et al.  Vaccines for Biodefense and Emerging and Neglected Diseases , 2009 .

[119]  A Flahault,et al.  Understanding the dynamics of Ebola epidemics , 2006, Epidemiology and Infection.

[120]  S. Rossiter,et al.  Contrasting Genetic Structure in Two Co-Distributed Species of Old World Fruit Bat , 2010, PloS one.

[121]  P. Formenty,et al.  Studies of Reservoir Hosts for Marburg Virus , 2007, Emerging infectious diseases.

[122]  M. E. Miranda,et al.  Reston ebolavirus in humans and animals in the Philippines: a review. , 2011, The Journal of infectious diseases.

[123]  J. Epstein,et al.  Pteropus vampyrus, a hunted migratory species with a multinational home‐range and a need for regional management , 2009 .

[124]  Heinz Feldmann,et al.  Ebola virus: from discovery to vaccine , 2003, Nature Reviews Immunology.

[125]  R. May,et al.  Population biology of infectious diseases: Part I , 1979, Nature.

[126]  L. Real,et al.  Recent Common Ancestry of Ebola Zaire Virus Found in a Bat Reservoir , 2006, PLoS pathogens.

[127]  J. Epstein,et al.  Risk Factors for Nipah Virus Infection among Pteropid Bats, Peninsular Malaysia , 2013, Emerging infectious diseases.

[128]  C. Schwegmann-Wessels,et al.  Differential Sensitivity of Bat Cells to Infection by Enveloped RNA Viruses: Coronaviruses, Paramyxoviruses, Filoviruses, and Influenza Viruses , 2013, PloS one.

[129]  M. Turell,et al.  Short report: lack of virus replication in arthropods after intrathoracic inoculation of Ebola Reston virus. , 1996, The American journal of tropical medicine and hygiene.

[130]  S. Hazar,et al.  Filoviridae: Marburg and Ebola viruses. , 2000 .

[131]  A. Peterson,et al.  Potential Mammalian Filovirus Reservoirs , 2004, Emerging infectious diseases.

[132]  Viral haemorrhagic fever in imported monkeys. , 1992, Releve epidemiologique hebdomadaire.

[133]  H. Feldmann,et al.  Biosynthesis and role of filoviral glycoproteins. , 2001, The Journal of general virology.

[134]  N. Wauquier,et al.  High Prevalence of Both Humoral and Cellular Immunity to Zaire ebolavirus among Rural Populations in Gabon , 2010, PloS one.

[135]  Alan Kemp,et al.  Marburg hemorrhagic fever associated with multiple genetic lineages of virus. , 2006, The New England journal of medicine.

[136]  T. Gojobori,et al.  The origin and evolution of Ebola and Marburg viruses. , 1997, Molecular biology and evolution.

[137]  G. Grard,et al.  Marburg Virus Infection Detected in a Common African Bat , 2007, PloS one.

[138]  Adam J. Hume,et al.  Forty-Five Years of Marburg Virus Research , 2012, Viruses.

[139]  P. Rollin,et al.  Ebola Reston virus infection of pigs: clinical significance and transmission potential. , 2011, The Journal of infectious diseases.

[140]  L. Real,et al.  Wave-Like Spread of Ebola Zaire , 2005, PLoS biology.

[141]  Stephen P. Luby,et al.  Ebola Virus Antibodies in Fruit Bats, Bangladesh , 2013, Emerging infectious diseases.

[142]  C. Broder,et al.  Use of cross-reactive serological assays for detecting novel pathogens in wildlife: assessing an appropriate cutoff for henipavirus assays in African bats. , 2013, Journal of virological methods.

[143]  J. Gonzalez,et al.  Fruit bats as reservoirs of Ebola virus , 2005, Nature.

[144]  C. Boesch,et al.  Isolation and partial characterisation of a new strain of Ebola virus , 1995, The Lancet.

[145]  C. D. de Jong,et al.  Establishment, Immortalisation and Characterisation of Pteropid Bat Cell Lines , 2009, PloS one.

[146]  J. A. Comer,et al.  Marburgvirus Genomics and Association with a Large Hemorrhagic Fever Outbreak in Angola , 2006, Journal of Virology.

[147]  Update: filovirus infection in animal handlers. , 1990, MMWR. Morbidity and mortality weekly report.

[148]  C. Rupprecht,et al.  Marburg Virus in Fruit Bat, Kenya , 2010, Emerging infectious diseases.

[149]  M. Colyn,et al.  Identification of Ebola virus sequences present as RNA or DNA in organs of terrestrial small mammals of the Central African Republic. , 1999, Microbes and infection.

[150]  Kate E. Jones,et al.  Global trends in emerging infectious diseases , 2008, Nature.

[151]  Arnold J. Levine,et al.  Unexpected Inheritance: Multiple Integrations of Ancient Bornavirus and Ebolavirus/Marburgvirus Sequences in Vertebrate Genomes , 2010, PLoS pathogens.