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8. Virus nomenclature below the species level: a standardized nomenclature for filovirus strains and variants rescued from cDNA

Author

Kuhn, Jens H., Bào, Yīmíng, Bavari, Sina, Becker, Stephan, Bradfute, Steven, Brauburger, Kristina, Rodney Brister, J., Bukreyev, Alexander A., Caì, Yíngyún, Chandran, Kartik, Davey, Robert A., Dolnik, Olga, Dye, John M., Enterlein, Sven, Gonzalez, Jean-Paul, Formenty, Pierre, Freiberg, Alexander N., Hensley, Lisa E., Hoenen, Thomas, Honko, Anna N., Ignatyev, Georgy M., Jahrling, Peter B., Johnson, Karl M., Klenk, Hans-Dieter, Kobinger, Gary, Lackemeyer, Matthew G., Leroy, Eric M., Lever, Mark S., Mühlberger, Elke, Netesov, Sergey V., Olinger, Gene G., Palacios, Gustavo, Patterson, Jean L., Paweska, Janusz T., Pitt, Louise, Radoshitzky, Sheli R., Ryabchikova, Elena I., Saphire, Erica Ollmann, Shestopalov, Aleksandr M., Smither, Sophie J., Sullivan, Nancy J., Swanepoel, Robert, Takada, Ayato, Towner, Jonathan S., van der Groen, Guido, Volchkov, Viktor E., Volchkova, Valentina A., Wahl-Jensen, Victoria, Warren, Travis K., Warfield, Kelly L., Weidmann, Manfred, and Nichol, Stuart T.

Published
2014
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9. Virus nomenclature below the species level: a standardized nomenclature for laboratory animal-adapted strains and variants of viruses assigned to the family Filoviridae

Author

Kuhn, Jens H., Bao, Yiming, Bavari, Sina, Becker, Stephan, Bradfute, Steven, Brister, J. Rodney, Bukreyev, Alexander A., Caì, Yíngyún, Chandran, Kartik, Davey, Robert A., Dolnik, Olga, Dye, John M., Enterlein, Sven, Gonzalez, Jean-Paul, Formenty, Pierre, Freiberg, Alexander N., Hensley, Lisa E., Honko, Anna N., Ignatyev, Georgy M., Jahrling, Peter B., Johnson, Karl M., Klenk, Hans-Dieter, Kobinger, Gary, Lackemeyer, Matthew G., Leroy, Eric M., Lever, Mark S., Lofts, Loreen L., Mühlberger, Elke, Netesov, Sergey V., Olinger, Gene G., Palacios, Gustavo, Patterson, Jean L., Paweska, Janusz T., Pitt, Louise, Radoshitzky, Sheli R., Ryabchikova, Elena I., Saphire, Erica Ollmann, Shestopalov, Aleksandr M., Smither, Sophie J., Sullivan, Nancy J., Swanepoel, Robert, Takada, Ayato, Towner, Jonathan S., van der Groen, Guido, Volchkov, Viktor E., Wahl-Jensen, Victoria, Warren, Travis K., Warfield, Kelly L., Weidmann, Manfred, and Nichol, Stuart T.

Published
2013
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10. Virus nomenclature below the species level: a standardized nomenclature for natural variants of viruses assigned to the family Filoviridae

Author

Kuhn, Jens H., Bao, Yiming, Bavari, Sina, Becker, Stephan, Bradfute, Steven, Brister, J. Rodney, Bukreyev, Alexander A., Chandran, Kartik, Davey, Robert A., Dolnik, Olga, Dye, John M., Enterlein, Sven, Hensley, Lisa E., Honko, Anna N., Jahrling, Peter B., Johnson, Karl M., Kobinger, Gary, Leroy, Eric M., Lever, Mark S., Mühlberger, Elke, Netesov, Sergey V., Olinger, Gene G., Palacios, Gustavo, Patterson, Jean L., Paweska, Janusz T., Pitt, Louise, Radoshitzky, Sheli R., Saphire, Erica Ollmann, Smither, Sophie J., Swanepoel, Robert, Towner, Jonathan S., van der Groen, Guido, Volchkov, Viktor E., Wahl-Jensen, Victoria, Warren, Travis K., Weidmann, Manfred, and Nichol, Stuart T.

Published
2013
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13. Investigative study into whether an insect repellent has virucidal activity against SARS-CoV-2

Author

Smither, Sophie J., primary, Eastaugh, Lin S., additional, Findlay, James S., additional, Laws, Thomas R., additional, Marriott, Stephen N., additional, Notman, Stuart, additional, O’Brien, Lyn M., additional, Phelps, Amanda L., additional, Richards, Mark, additional, Ulaeto, David, additional, Watts, Pat, additional, Lever, Mark S., additional, and Govan, Norman, additional

Published
2021
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23. Filovirus RefSeq Entries: Evaluation and Selection of Filovirus Type Variants, Type Sequences, and Names

Author

Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Kuhn, Jens H., Andersen, Kristian G., Bào, Yīmíng, Bavari, Sina, Becker, Stephan, Bennett, Richard S., Bergman, Nicholas H., Blinkova, Olga, Bradfute, Steven, Brister, J. Rodney, Bukreyev, Alexander, Chandran, Kartik, Chepurnov, Alexander A., Davey, Robert A., Dietzgen, Ralf G., Doggett, Norman A., Dolnik, Olga, Dye, John M., Enterlein, Sven, Fenimore, Paul W., Formenty, Pierre, Freiberg, Alexander N., Garry, Robert F., Garza, Nicole L., Gire, Stephen K., Gonzalez, Jean-Paul, Griffiths, Anthony, Happi, Christian T., Hensley, Lisa E., Herbert, Andrew S., Hevey, Michael C., Hoenen, Thomas, Honko, Anna N., Ignatyev, Georgy M., Jahrling, Peter B., Johnson, Joshua C., Johnson, Karl M., Kindrachuk, Jason, Klenk, Hans-Dieter, Kobinger, Gary, Kochel, Tadeusz J., Lackemeyer, Matthew G., Lackner, Daniel F., Leroy, Eric M., Lever, Mark S., Mühlberger, Elke, Netesov, Sergey V., Olinger, Gene G., Omilabu, Sunday A., Palacios, Gustavo, Panchal, Rekha G., Park, Daniel J., Patterson, Jean L., Paweska, Janusz T., Peters, Clarence J., Pettitt, James, Pitt, Louise, Radoshitzky, Sheli R., Ryabchikova, Elena I., Saphire, Erica Ollmann, Sabeti, Pardis C., Sealfon, Rachel Sima, Shestopalov, Aleksandr M., Smither, Sophie J., Sullivan, Nancy J., Swanepoel, Robert, Takada, Ayato, Towner, Jonathan S., Van der Groen, Guido, Volchkov, Viktor E., Volchkova, Valentina A., Wahl-Jensen, Victoria, Warren, Travis K., Warfield, Kelly L., Weidmann, Manfred, Nichol, Stuart T., Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Kuhn, Jens H., Andersen, Kristian G., Bào, Yīmíng, Bavari, Sina, Becker, Stephan, Bennett, Richard S., Bergman, Nicholas H., Blinkova, Olga, Bradfute, Steven, Brister, J. Rodney, Bukreyev, Alexander, Chandran, Kartik, Chepurnov, Alexander A., Davey, Robert A., Dietzgen, Ralf G., Doggett, Norman A., Dolnik, Olga, Dye, John M., Enterlein, Sven, Fenimore, Paul W., Formenty, Pierre, Freiberg, Alexander N., Garry, Robert F., Garza, Nicole L., Gire, Stephen K., Gonzalez, Jean-Paul, Griffiths, Anthony, Happi, Christian T., Hensley, Lisa E., Herbert, Andrew S., Hevey, Michael C., Hoenen, Thomas, Honko, Anna N., Ignatyev, Georgy M., Jahrling, Peter B., Johnson, Joshua C., Johnson, Karl M., Kindrachuk, Jason, Klenk, Hans-Dieter, Kobinger, Gary, Kochel, Tadeusz J., Lackemeyer, Matthew G., Lackner, Daniel F., Leroy, Eric M., Lever, Mark S., Mühlberger, Elke, Netesov, Sergey V., Olinger, Gene G., Omilabu, Sunday A., Palacios, Gustavo, Panchal, Rekha G., Park, Daniel J., Patterson, Jean L., Paweska, Janusz T., Peters, Clarence J., Pettitt, James, Pitt, Louise, Radoshitzky, Sheli R., Ryabchikova, Elena I., Saphire, Erica Ollmann, Sabeti, Pardis C., Sealfon, Rachel Sima, Shestopalov, Aleksandr M., Smither, Sophie J., Sullivan, Nancy J., Swanepoel, Robert, Takada, Ayato, Towner, Jonathan S., Van der Groen, Guido, Volchkov, Viktor E., Volchkova, Valentina A., Wahl-Jensen, Victoria, Warren, Travis K., Warfield, Kelly L., Weidmann, Manfred, and Nichol, Stuart T.

Abstract

Sequence determination of complete or coding-complete genomes of viruses is becoming common practice for supporting the work of epidemiologists, ecologists, virologists, and taxonomists. Sequencing duration and costs are rapidly decreasing, sequencing hardware is under modification for use by non-experts, and software is constantly being improved to simplify sequence data management and analysis. Thus, analysis of virus disease outbreaks on the molecular level is now feasible, including characterization of the evolution of individual virus populations in single patients over time. The increasing accumulation of sequencing data creates a management problem for the curators of commonly used sequence databases and an entry retrieval problem for end users. Therefore, utilizing the data to their fullest potential will require setting nomenclature and annotation standards for virus isolates and associated genomic sequences. The National Center for Biotechnology Information’s (NCBI’s) RefSeq is a non-redundant, curated database for reference (or type) nucleotide sequence records that supplies source data to numerous other databases. Building on recently proposed templates for filovirus variant naming [ ()/<;isolation host-suffix>///-], we report consensus decisions from a majority of past and currently active filovirus experts on the eight filovirus type variants and isolates to be represented in RefSeq, their final designations, and their associated sequences. Keywords: Bundibugyo virus; cDNA clone; cuevavirus; Ebola; Ebola virus; ebolavirus; filovirid; Filoviridae; filovirus; genome annotation; ICTV; International Committee on Taxonomy of Viruses; Lloviu virus; Marburg virus; marburgvirus; mononegavirad; Mononegavirales; mononegavirus; Ravn virus; RefSeq; Reston virus; reverse genetics; Sudan virus; Taï Forest virus; virus classification; virus isolate; virus nome

Published
2019

27. Experimental respiratory anthrax infection in the common marmoset (Callithrix jacchus)

Author

Lever, Mark S, Stagg, Anthony J, Nelson, Michelle, Pearce, Peter, Stevens, Daniel J, Scott, Elizabeth A M, Simpson, Andrew J H, and Fulop, Mark J

Subjects
Aerosols, Male, Inhalation Exposure, Virulence, animal diseases, fungi, Body Weight, Colony Count, Microbial, Callithrix, Original Articles, humanities, Anthrax, Lethal Dose 50, Disease Models, Animal, Bacillus anthracis, Animals, Female, Respiratory Tract Infections
Abstract

Inhalational anthrax is a rare but potentially fatal infection in man. The common marmoset (Callithrix jacchus) was evaluated as a small non-human primate (NHP) model of inhalational anthrax infection, as an alternative to larger NHP species. The marmoset was found to be susceptible to inhalational exposure to Bacillus anthracis Ames strain. The pathophysiology of infection following inhalational exposure was similar to that previously reported in the rhesus and cynomolgus macaque and humans. The calculated LD(50) for B. anthracis Ames strain in the marmoset was 1.47 x 10(3) colony-forming units, compared with a published LD(50) of 5.5 x 10(4) spores in the rhesus macaque and 4.13 x 10(3) spores in the cynomolgus macaque. This suggests that the common marmoset is an appropriate alternative NHP and will be used for the evaluation of medical countermeasures against respiratory anthrax infection.

Published
2008

28. Susceptibility and Lethality of Western Equine Encephalitis Virus in Balb/c Mice When Infected by the Aerosol Route.

Author

Phelps, Amanda L., O'Brien, Lyn M., Eastaugh, Lin S., Davies, Carwyn, Lever, Mark S., Ennis, Jane, Zeitlin, Larry, Nunez, Alejandro, and Ulaeto, David O.

Subjects
EQUINE encephalomyelitis, COMMUNICABLE diseases in animals, PANDEMICS, MICE, AEROSOLS, MICROBIAL virulence
Abstract

Western equine encephalitis virus (WEEV) naturally cycles between mosquitos and birds or rodents, with a case fatality rate of up to 15% in humans during epizootic outbreaks. There are no medical countermeasures to treat WEEV infection, and accidental aerosol exposure increases the case fatality rate up to 40%. Understanding the pathogenesis of infection is required to develop and assess medical countermeasures. This study describes the clinical and pathological findings of mice infected with WEEV by the aerosol route, and use as a model for WEEV infection in humans. Balb/c mice were infected by the aerosol route with a dose range of high-virulence WEEV strain Fleming to establish the median lethal dose (MLD). The disease course was acute, culminating in severe clinical signs, neuroinvasion, and dose-dependent mortality. Further groups of mice were exposed by the aerosol route, periodically sacrificed, and tissues excised for histopathological examination and virology. Viral titres peaked four days post-challenge in the brain and lungs, corresponding with severe bilateral lesions in rostroventral regions of the encephalon, especially in the olfactory bulb and piriform cortex. Recapitulation of the most serious clinical presentations of human WEEV disease in mice may prove a useful tool in the evaluation of medical countermeasures. [ABSTRACT FROM AUTHOR]

Published
2017
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29. Reidentification of Ebola Virus E718 and ME as Ebola Virus/H.sapiens-tc/COD/1976/Yambuku-Ecran

Author

Kuhn, Jens H., primary, Lofts, Loreen L., additional, Kugelman, Jeffrey R., additional, Smither, Sophie J., additional, Lever, Mark S., additional, van der Groen, Guido, additional, Johnson, Karl M., additional, Radoshitzky, Sheli R., additional, Bavari, Sina, additional, Jahrling, Peter B., additional, Towner, Jonathan S., additional, Nichol, Stuart T., additional, and Palacios, Gustavo, additional

Published
2014
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30. Virus nomenclature below the species level: a standardized nomenclature for filovirus strains and variants rescued from cDNA

Author

Kuhn, Jens H., primary, Bào, Yīmíng, additional, Bavari, Sina, additional, Becker, Stephan, additional, Bradfute, Steven, additional, Brauburger, Kristina, additional, Rodney Brister, J., additional, Bukreyev, Alexander A., additional, Caì, Yíngyún, additional, Chandran, Kartik, additional, Davey, Robert A., additional, Dolnik, Olga, additional, Dye, John M., additional, Enterlein, Sven, additional, Gonzalez, Jean-Paul, additional, Formenty, Pierre, additional, Freiberg, Alexander N., additional, Hensley, Lisa E., additional, Hoenen, Thomas, additional, Honko, Anna N., additional, Ignatyev, Georgy M., additional, Jahrling, Peter B., additional, Johnson, Karl M., additional, Klenk, Hans-Dieter, additional, Kobinger, Gary, additional, Lackemeyer, Matthew G., additional, Leroy, Eric M., additional, Lever, Mark S., additional, Mühlberger, Elke, additional, Netesov, Sergey V., additional, Olinger, Gene G., additional, Palacios, Gustavo, additional, Patterson, Jean L., additional, Paweska, Janusz T., additional, Pitt, Louise, additional, Radoshitzky, Sheli R., additional, Ryabchikova, Elena I., additional, Saphire, Erica Ollmann, additional, Shestopalov, Aleksandr M., additional, Smither, Sophie J., additional, Sullivan, Nancy J., additional, Swanepoel, Robert, additional, Takada, Ayato, additional, Towner, Jonathan S., additional, van der Groen, Guido, additional, Volchkov, Viktor E., additional, Volchkova, Valentina A., additional, Wahl-Jensen, Victoria, additional, Warren, Travis K., additional, Warfield, Kelly L., additional, Weidmann, Manfred, additional, and Nichol, Stuart T., additional

Published
2013
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31. Virus nomenclature below the species level: a standardized nomenclature for natural variants of viruses assigned to the family Filoviridae

Author

Kuhn, Jens H., primary, Bao, Yiming, additional, Bavari, Sina, additional, Becker, Stephan, additional, Bradfute, Steven, additional, Brister, J. Rodney, additional, Bukreyev, Alexander A., additional, Chandran, Kartik, additional, Davey, Robert A., additional, Dolnik, Olga, additional, Dye, John M., additional, Enterlein, Sven, additional, Hensley, Lisa E., additional, Honko, Anna N., additional, Jahrling, Peter B., additional, Johnson, Karl M., additional, Kobinger, Gary, additional, Leroy, Eric M., additional, Lever, Mark S., additional, Mühlberger, Elke, additional, Netesov, Sergey V., additional, Olinger, Gene G., additional, Palacios, Gustavo, additional, Patterson, Jean L., additional, Paweska, Janusz T., additional, Pitt, Louise, additional, Radoshitzky, Sheli R., additional, Saphire, Erica Ollmann, additional, Smither, Sophie J., additional, Swanepoel, Robert, additional, Towner, Jonathan S., additional, van der Groen, Guido, additional, Volchkov, Viktor E., additional, Wahl-Jensen, Victoria, additional, Warren, Travis K., additional, Weidmann, Manfred, additional, and Nichol, Stuart T., additional

Published
2012
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37. Bioavailability and Efficacy of Levofloxacin against Francisella tularensisin the Common Marmoset (Callithrix jacchus)

Author

Nelson, Michelle, Lever, Mark S., Dean, Rachel E., Pearce, Peter C., Stevens, Daniel J., and Simpson, Andrew J. H.

Abstract

ABSTRACTPharmacokinetic and efficacy studies with levofloxacin were performed in the common marmoset (Callithrix jacchus) model of inhalational tularemia. Plasma levofloxacin pharmacokinetics were determined in six animals in separate single-dose and multidose studies. Plasma drug concentrations were analyzed using liquid chromatography-tandem mass spectrometry-electrospray ionization. On day 7 of a twice-daily dosing regimen of 40 mg/kg, the levofloxacin half-life, maximum concentration, and area under the curve in marmoset plasma were 2.3 h, 20.9 μg/ml, and 81.4 μg/liter/h, respectively. An efficacy study was undertaken using eight treated and two untreated control animals. Marmosets were challenged with a mean of 1.5 × 102CFU of Francisella tularensisby the airborne route. Treated animals were administered 16.5 mg/kg levofloxacin by mouth twice daily, based on the pharmacokinetic parameters, beginning 24 h after challenge. Control animals had a raised core body temperature by 57 h postchallenge and died from infection by day 5. All of the other animals survived, remained afebrile, and lacked overt clinical signs. No bacteria were recovered from the organs of these animals at postmortem after culling at day 24 postchallenge. In conclusion, postexposure prophylaxis with orally administered levofloxacin was efficacious against acute inhalational tularemia in the common marmoset. The marmoset appears to be an appropriate animal model for the evaluation of postexposure therapies.

Published
2010
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38. Filovirus RefSeq Entries: Evaluation and Selection of Filovirus Type Variants, Type Sequences, and Names

Author

Kuhn, Jens H., Andersen, Kristian G., Bào, Yīmíng, Bavari, Sina, Becker, Stephan, Bennett, Richard S., Bergman, Nicholas H., Blinkova, Olga, Bradfute, Steven, Brister, J. Rodney, Bukreyev, Alexander, Chandran, Kartik, Chepurnov, Alexander A., Davey, Robert A., Dietzgen, Ralf G., Doggett, Norman A., Dolnik, Olga, Dye, John M., Enterlein, Sven, Fenimore, Paul W., Formenty, Pierre, Freiberg, Alexander N., Garry, Robert F., Garza, Nicole L., Gire, Stephen K., Gonzalez, Jean-Paul, Griffiths, Anthony, Happi, Christian T., Hensley, Lisa E., Herbert, Andrew S., Hevey, Michael C., Hoenen, Thomas, Honko, Anna N., Ignatyev, Georgy M., Jahrling, Peter B., Johnson, Joshua C., Johnson, Karl M., Kindrachuk, Jason, Klenk, Hans-Dieter, Kobinger, Gary, Kochel, Tadeusz J., Lackemeyer, Matthew G., Lackner, Daniel F., Leroy, Eric M., Lever, Mark S., Mühlberger, Elke, Netesov, Sergey V., Olinger, Gene G., Omilabu, Sunday A., Palacios, Gustavo, Panchal, Rekha G., Park, Daniel J., Patterson, Jean L., Paweska, Janusz T., Peters, Clarence J., Pettitt, James, Pitt, Louise, Radoshitzky, Sheli R., Ryabchikova, Elena I., Saphire, Erica Ollmann, Sabeti, Pardis C., Sealfon, Rachel, Shestopalov, Aleksandr M., Smither, Sophie J., Sullivan, Nancy J., Swanepoel, Robert, Takada, Ayato, Towner, Jonathan S., van der Groen, Guido, Volchkov, Viktor E., Volchkova, Valentina A., Wahl-Jensen, Victoria, Warren, Travis K., Warfield, Kelly L., Weidmann, Manfred, and Nichol, Stuart T.

Subjects
Bundibugyo virus, cDNA clone, cuevavirus, Ebola, Ebola virus, ebolavirus, filovirid, filovirus, genome annotation, ICTV, International Committee on Taxonomy of Viruses, Lloviu virus, Marburg virus, marburgvirus, mononegavirad, mononegavirus, Ravn virus, RefSeq, Reston virus, reverse genetics, Sudan virus, Taï Forest virus, virus classification, virus isolate, virus nomenclature, virus strain, virus taxonomy, virus variant
Abstract

Sequence determination of complete or coding-complete genomes of viruses is becoming common practice for supporting the work of epidemiologists, ecologists, virologists, and taxonomists. Sequencing duration and costs are rapidly decreasing, sequencing hardware is under modification for use by non-experts, and software is constantly being improved to simplify sequence data management and analysis. Thus, analysis of virus disease outbreaks on the molecular level is now feasible, including characterization of the evolution of individual virus populations in single patients over time. The increasing accumulation of sequencing data creates a management problem for the curators of commonly used sequence databases and an entry retrieval problem for end users. Therefore, utilizing the data to their fullest potential will require setting nomenclature and annotation standards for virus isolates and associated genomic sequences. The National Center for Biotechnology Information’s (NCBI’s) RefSeq is a non-redundant, curated database for reference (or type) nucleotide sequence records that supplies source data to numerous other databases. Building on recently proposed templates for filovirus variant naming [ ()////-], we report consensus decisions from a majority of past and currently active filovirus experts on the eight filovirus type variants and isolates to be represented in RefSeq, their final designations, and their associated sequences.

Published
2014
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39. Lethality and pathogenesis of airborne infection with filoviruses in A129 α/β -/- interferon receptor-deficient mice.

Author

Lever MS, Piercy TJ, Steward JA, Eastaugh L, Smither SJ, Taylor C, Salguero FJ, and Phillpotts RJ

Subjects
Animals, Ebolavirus pathogenicity, Female, Filoviridae classification, Filoviridae Infections virology, Hemorrhagic Fever, Ebola mortality, Hemorrhagic Fever, Ebola physiopathology, Hemorrhagic Fever, Ebola virology, Humans, Injections, Intraperitoneal, Male, Marburg Virus Disease mortality, Marburg Virus Disease physiopathology, Marburg Virus Disease virology, Marburgvirus pathogenicity, Mice, Mice, Knockout, Receptor, Interferon alpha-beta deficiency, Virulence, Aerosols, Disease Models, Animal, Filoviridae pathogenicity, Filoviridae Infections mortality, Filoviridae Infections physiopathology, Receptor, Interferon alpha-beta genetics
Abstract

Normal immunocompetent mice are not susceptible to non-adapted filoviruses. There are therefore two strategies available to establish a murine model of filovirus infection: adaptation of the virus to the host or the use of genetically modified mice that are susceptible to the virus. A number of knockout (KO) strains of mice with defects in either their adaptive or innate immunity are susceptible to non-adapted filoviruses. In this study, A129 α/β -/- interferon receptor-deficient KO mice, strain A129 IFN-α/β -/-, were used to determine the lethality of a range of filoviruses, including Lake Victoria marburgvirus (MARV), Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV), Reston ebolavirus (REBOV) and Côte d'Ivoire ebolavirus (CIEBOV), administered by using intraperitoneal (IP) or aerosol routes of infection. One hundred percent mortality was observed in all groups of KO mice that were administered with a range of challenge doses of MARV and ZEBOV by either IP or aerosol routes. Mean time to death for both routes was dose-dependent and ranged from 5.4 to 7.4 days in the IP injection challenge, and from 10.2 to 13 days in the aerosol challenge. The lethal dose (50 % tissue culture infective dose, TCID(50)) of ZEBOV for KO mice was <1 TCID(50) ml(-1) when administered by either the IP or aerosol route of infection; for MARV the lethal dose was <1 TCID(50) ml(-1) by the IP route of infection and <10 TCID(50) ml(-1) by the aerosol route. In contrast, there was no mortality after infection with SEBOV or REBOV by either IP or aerosol routes of infection; all the mice lost weight (~15 % loss of group mean body weight with SEBOV and ~7 % with REBOV) but recovered to their original weights by day 14 post-challenge. There was no mortality in mice administered with CIEBOV via the IP route of infection and no clinical signs of infection were observed. The progression of disease was faster following infection with ZEBOV than with MARV but ultimately both viruses caused widespread infection with high titres of the infectious viruses in multiple organs. Histopathological observations were consistent with other animal models and showed widespread organ damage. This study suggests that MARV and ZEBOV are more virulent when administered via the IP route rather than by aerosol infection, although both are highly virulent by either route. The KO mouse may provide a useful model to test potential antiviral therapeutics against wild-type filoviruses.

Published
2012
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