On-Demand Patient-Specific Phenotype-to-Genotype Ebola Virus Characterization
Biosafety, biosecurity, logistical, political, and technical considerations can delay or prevent the wide dissemination of source material containing viable virus from the geographic origin of an outbreak to laboratories involved in developing medical countermeasures (MCMs). However, once virus geno...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/10/2010 |
| _version_ | 1797512898515304448 |
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| author | Brett F. Beitzel Sheli R. Radoshitzky Nicholas Di Paola Jennifer M. Brannan David Kimmel Katie Caviness Veronica Soloveva Shuiqing Yu Elena N. Postnikova Courtney L. Finch Hu Liu Laura Prugar Russell Bakken John M. Dye Jeffrey R. Kugelman James M. Cunningham Mariano Sanchez-Lockhart Jens H. Kuhn Gustavo Palacios |
| author_facet | Brett F. Beitzel Sheli R. Radoshitzky Nicholas Di Paola Jennifer M. Brannan David Kimmel Katie Caviness Veronica Soloveva Shuiqing Yu Elena N. Postnikova Courtney L. Finch Hu Liu Laura Prugar Russell Bakken John M. Dye Jeffrey R. Kugelman James M. Cunningham Mariano Sanchez-Lockhart Jens H. Kuhn Gustavo Palacios |
| author_sort | Brett F. Beitzel |
| collection | DOAJ |
| description | Biosafety, biosecurity, logistical, political, and technical considerations can delay or prevent the wide dissemination of source material containing viable virus from the geographic origin of an outbreak to laboratories involved in developing medical countermeasures (MCMs). However, once virus genome sequence information is available from clinical samples, reverse-genetics systems can be used to generate virus stocks de novo to initiate MCM development. In this study, we developed a reverse-genetics system for natural isolates of Ebola virus (EBOV) variants Makona, Tumba, and Ituri, which have been challenging to obtain. These systems were generated starting solely with in silico genome sequence information and have been used successfully to produce recombinant stocks of each of the viruses for use in MCM testing. The antiviral activity of MCMs targeting viral entry varied depending on the recombinant virus isolate used. Collectively, selecting and synthetically engineering emerging EBOV variants and demonstrating their efficacy against available MCMs will be crucial for answering pressing public health and biosecurity concerns during Ebola disease (EBOD) outbreaks. |
| first_indexed | 2024-03-10T06:08:08Z |
| format | Article |
| id | doaj.art-0ee43d4ed623440aa0b0b3157867c4e1 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T06:08:08Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-0ee43d4ed623440aa0b0b3157867c4e12023-11-22T20:19:23ZengMDPI AGViruses1999-49152021-10-011310201010.3390/v13102010On-Demand Patient-Specific Phenotype-to-Genotype Ebola Virus CharacterizationBrett F. Beitzel0Sheli R. Radoshitzky1Nicholas Di Paola2Jennifer M. Brannan3David Kimmel4Katie Caviness5Veronica Soloveva6Shuiqing Yu7Elena N. Postnikova8Courtney L. Finch9Hu Liu10Laura Prugar11Russell Bakken12John M. Dye13Jeffrey R. Kugelman14James M. Cunningham15Mariano Sanchez-Lockhart16Jens H. Kuhn17Gustavo Palacios18United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USAIntegrated Research Facility at Fort Detrick (IRF-Frederick), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Fort Detrick, Frederick, MD 21702, USAIntegrated Research Facility at Fort Detrick (IRF-Frederick), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Fort Detrick, Frederick, MD 21702, USAIntegrated Research Facility at Fort Detrick (IRF-Frederick), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Fort Detrick, Frederick, MD 21702, USADepartment of Medicine, Brigham and Women’s Hospital and Department of Microbiology, Harvard Medical School, Boston, MA 02115, USAUnited States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USADepartment of Medicine, Brigham and Women’s Hospital and Department of Microbiology, Harvard Medical School, Boston, MA 02115, USAUnited States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USAIntegrated Research Facility at Fort Detrick (IRF-Frederick), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USABiosafety, biosecurity, logistical, political, and technical considerations can delay or prevent the wide dissemination of source material containing viable virus from the geographic origin of an outbreak to laboratories involved in developing medical countermeasures (MCMs). However, once virus genome sequence information is available from clinical samples, reverse-genetics systems can be used to generate virus stocks de novo to initiate MCM development. In this study, we developed a reverse-genetics system for natural isolates of Ebola virus (EBOV) variants Makona, Tumba, and Ituri, which have been challenging to obtain. These systems were generated starting solely with in silico genome sequence information and have been used successfully to produce recombinant stocks of each of the viruses for use in MCM testing. The antiviral activity of MCMs targeting viral entry varied depending on the recombinant virus isolate used. Collectively, selecting and synthetically engineering emerging EBOV variants and demonstrating their efficacy against available MCMs will be crucial for answering pressing public health and biosecurity concerns during Ebola disease (EBOD) outbreaks.https://www.mdpi.com/1999-4915/13/10/2010Ebola virusEBOVreverse geneticsgenotype-to-phenotypevariantson-demand |
| spellingShingle | Brett F. Beitzel Sheli R. Radoshitzky Nicholas Di Paola Jennifer M. Brannan David Kimmel Katie Caviness Veronica Soloveva Shuiqing Yu Elena N. Postnikova Courtney L. Finch Hu Liu Laura Prugar Russell Bakken John M. Dye Jeffrey R. Kugelman James M. Cunningham Mariano Sanchez-Lockhart Jens H. Kuhn Gustavo Palacios On-Demand Patient-Specific Phenotype-to-Genotype Ebola Virus Characterization Viruses Ebola virus EBOV reverse genetics genotype-to-phenotype variants on-demand |
| title | On-Demand Patient-Specific Phenotype-to-Genotype Ebola Virus Characterization |
| title_full | On-Demand Patient-Specific Phenotype-to-Genotype Ebola Virus Characterization |
| title_fullStr | On-Demand Patient-Specific Phenotype-to-Genotype Ebola Virus Characterization |
| title_full_unstemmed | On-Demand Patient-Specific Phenotype-to-Genotype Ebola Virus Characterization |
| title_short | On-Demand Patient-Specific Phenotype-to-Genotype Ebola Virus Characterization |
| title_sort | on demand patient specific phenotype to genotype ebola virus characterization |
| topic | Ebola virus EBOV reverse genetics genotype-to-phenotype variants on-demand |
| url | https://www.mdpi.com/1999-4915/13/10/2010 |
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