A Simple and Robust Approach for Evaluation of Antivirals Using a Recombinant Influenza Virus Expressing Gaussia Luciferase
Influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are major public health concerns. Because the effectiveness of seasonal vaccines is highly variable and the currently available drugs are limited in their efficacy because of the emergence of drug resis...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-06-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/10/6/325 |
| _version_ | 1818911581967220736 |
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| author | Ping Li Qinghua Cui Lin Wang Xiujuan Zhao Yingying Zhang Balaji Manicassamy Yong Yang Lijun Rong Ruikun Du |
| author_facet | Ping Li Qinghua Cui Lin Wang Xiujuan Zhao Yingying Zhang Balaji Manicassamy Yong Yang Lijun Rong Ruikun Du |
| author_sort | Ping Li |
| collection | DOAJ |
| description | Influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are major public health concerns. Because the effectiveness of seasonal vaccines is highly variable and the currently available drugs are limited in their efficacy because of the emergence of drug resistance, there is an urgent need to develop novel antivirals. In this study, we characterized a recombinant IAV-carrying Gaussia luciferase (Gluc) gene and determined its potential as a tool for evaluating therapeutics. We demonstrated that this recombinant IAV is replication-competent in tissue culture and pathogenic in mice, although it is slightly attenuated compared to the parental virus. Luciferase expression correlated well with virus propagation both in vitro and in vivo, providing a simple measure for viral replication in tissue culture and in mouse lungs. To demonstrate the utility of this virus, ribavirin and oseltamivir phosphate were used to treat the IAV-infected cells and mice, and we observed the dose-dependent inhibition of viral replication by a luciferase assay. Moreover, the decreased luciferase expression in the infected lungs could predict the protective efficacy of antiviral interventions as early as day 2 post virus challenge. In summary, this study provides a new and quantitative approach to evaluate antivirals against IAV. |
| first_indexed | 2024-12-19T23:00:59Z |
| format | Article |
| id | doaj.art-6bb8ba3fd38a4637882a696380b14f59 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-19T23:00:59Z |
| publishDate | 2018-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-6bb8ba3fd38a4637882a696380b14f592022-12-21T20:02:31ZengMDPI AGViruses1999-49152018-06-0110632510.3390/v10060325v10060325A Simple and Robust Approach for Evaluation of Antivirals Using a Recombinant Influenza Virus Expressing Gaussia LuciferasePing Li0Qinghua Cui1Lin Wang2Xiujuan Zhao3Yingying Zhang4Balaji Manicassamy5Yong Yang6Lijun Rong7Ruikun Du8College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, ChinaCollege of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, ChinaCollege of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, ChinaCollege of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, ChinaShandong Provincial Collaborative Innovation Center for Antiviral Traditional Chinese Medicine, Jinan 250355, ChinaDepartment of Microbiology, University of Chicago, Chicago, IL 60637, USAShandong Provincial Collaborative Innovation Center for Antiviral Traditional Chinese Medicine, Jinan 250355, ChinaDepartment of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USACollege of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, ChinaInfluenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are major public health concerns. Because the effectiveness of seasonal vaccines is highly variable and the currently available drugs are limited in their efficacy because of the emergence of drug resistance, there is an urgent need to develop novel antivirals. In this study, we characterized a recombinant IAV-carrying Gaussia luciferase (Gluc) gene and determined its potential as a tool for evaluating therapeutics. We demonstrated that this recombinant IAV is replication-competent in tissue culture and pathogenic in mice, although it is slightly attenuated compared to the parental virus. Luciferase expression correlated well with virus propagation both in vitro and in vivo, providing a simple measure for viral replication in tissue culture and in mouse lungs. To demonstrate the utility of this virus, ribavirin and oseltamivir phosphate were used to treat the IAV-infected cells and mice, and we observed the dose-dependent inhibition of viral replication by a luciferase assay. Moreover, the decreased luciferase expression in the infected lungs could predict the protective efficacy of antiviral interventions as early as day 2 post virus challenge. In summary, this study provides a new and quantitative approach to evaluate antivirals against IAV.http://www.mdpi.com/1999-4915/10/6/325influenza A virusGaussia luciferaseantiviraltherapeutics |
| spellingShingle | Ping Li Qinghua Cui Lin Wang Xiujuan Zhao Yingying Zhang Balaji Manicassamy Yong Yang Lijun Rong Ruikun Du A Simple and Robust Approach for Evaluation of Antivirals Using a Recombinant Influenza Virus Expressing Gaussia Luciferase Viruses influenza A virus Gaussia luciferase antiviral therapeutics |
| title | A Simple and Robust Approach for Evaluation of Antivirals Using a Recombinant Influenza Virus Expressing Gaussia Luciferase |
| title_full | A Simple and Robust Approach for Evaluation of Antivirals Using a Recombinant Influenza Virus Expressing Gaussia Luciferase |
| title_fullStr | A Simple and Robust Approach for Evaluation of Antivirals Using a Recombinant Influenza Virus Expressing Gaussia Luciferase |
| title_full_unstemmed | A Simple and Robust Approach for Evaluation of Antivirals Using a Recombinant Influenza Virus Expressing Gaussia Luciferase |
| title_short | A Simple and Robust Approach for Evaluation of Antivirals Using a Recombinant Influenza Virus Expressing Gaussia Luciferase |
| title_sort | simple and robust approach for evaluation of antivirals using a recombinant influenza virus expressing gaussia luciferase |
| topic | influenza A virus Gaussia luciferase antiviral therapeutics |
| url | http://www.mdpi.com/1999-4915/10/6/325 |
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