A Productive Expression Platform Derived from Host-Restricted Eilat Virus: Its Extensive Validation and Novel Strategy
Most alphaviruses are transmitted by mosquitoes and infect a wide range of insects and vertebrates. However, Eilat virus (EILV) is defective for infecting vertebrate cells at multiple levels of the viral life cycle. This host-restriction property renders EILV an attractive expression platform since...
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| Format: | Article |
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MDPI AG
2021-04-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/4/660 |
| _version_ | 1827695371030102016 |
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| author | Lu Tan Yiwen Zhang Xingxing Wang Dal Young Kim |
| author_facet | Lu Tan Yiwen Zhang Xingxing Wang Dal Young Kim |
| author_sort | Lu Tan |
| collection | DOAJ |
| description | Most alphaviruses are transmitted by mosquitoes and infect a wide range of insects and vertebrates. However, Eilat virus (EILV) is defective for infecting vertebrate cells at multiple levels of the viral life cycle. This host-restriction property renders EILV an attractive expression platform since it is not infectious for vertebrates and therefore provides a highly advantageous safety profile. Here, we investigated the feasibility of versatile EILV-based expression vectors. By replacing the structural genes of EILV with those of other alphaviruses, we generated seven different chimeras. These chimeras were readily rescued in the original mosquito cells and were able to reach high titers, suggesting that EILV is capable of packaging the structural proteins of different lineages. We also explored the ability of EILV to express authentic antigens via double subgenomic (SG) RNA vectors. Four foreign genetic materials of varied length were introduced into the EILV genome, and the expressed heterologous genetic materials were readily detected in the infected cells. By inserting an additional SG promoter into the chimera genome containing the structural genes of Chikungunya virus (CHIKV), we developed a bivalent vaccine candidate against CHIKV and Zika virus. These data demonstrate the outstanding compatibility of the EILV genome. The produced recombinants can be applied to vaccine and diagnostic tool development, but more investigations are required. |
| first_indexed | 2024-03-10T12:25:27Z |
| format | Article |
| id | doaj.art-c6b5a0a0339e45ba8a6b0b73c70e6c8f |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T12:25:27Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-c6b5a0a0339e45ba8a6b0b73c70e6c8f2023-11-21T15:06:38ZengMDPI AGViruses1999-49152021-04-0113466010.3390/v13040660A Productive Expression Platform Derived from Host-Restricted Eilat Virus: Its Extensive Validation and Novel StrategyLu Tan0Yiwen Zhang1Xingxing Wang2Dal Young Kim3Department of Infectious Diseases and Public Health, Jockey Club of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong 999077, ChinaDepartment of Infectious Diseases and Public Health, Jockey Club of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong 999077, ChinaDepartment of Infectious Diseases and Public Health, Jockey Club of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong 999077, ChinaDepartment of Infectious Diseases and Public Health, Jockey Club of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong 999077, ChinaMost alphaviruses are transmitted by mosquitoes and infect a wide range of insects and vertebrates. However, Eilat virus (EILV) is defective for infecting vertebrate cells at multiple levels of the viral life cycle. This host-restriction property renders EILV an attractive expression platform since it is not infectious for vertebrates and therefore provides a highly advantageous safety profile. Here, we investigated the feasibility of versatile EILV-based expression vectors. By replacing the structural genes of EILV with those of other alphaviruses, we generated seven different chimeras. These chimeras were readily rescued in the original mosquito cells and were able to reach high titers, suggesting that EILV is capable of packaging the structural proteins of different lineages. We also explored the ability of EILV to express authentic antigens via double subgenomic (SG) RNA vectors. Four foreign genetic materials of varied length were introduced into the EILV genome, and the expressed heterologous genetic materials were readily detected in the infected cells. By inserting an additional SG promoter into the chimera genome containing the structural genes of Chikungunya virus (CHIKV), we developed a bivalent vaccine candidate against CHIKV and Zika virus. These data demonstrate the outstanding compatibility of the EILV genome. The produced recombinants can be applied to vaccine and diagnostic tool development, but more investigations are required.https://www.mdpi.com/1999-4915/13/4/660Eilat virusexpression platforminsect-specificdiagnostic toolvaccine candidate |
| spellingShingle | Lu Tan Yiwen Zhang Xingxing Wang Dal Young Kim A Productive Expression Platform Derived from Host-Restricted Eilat Virus: Its Extensive Validation and Novel Strategy Viruses Eilat virus expression platform insect-specific diagnostic tool vaccine candidate |
| title | A Productive Expression Platform Derived from Host-Restricted Eilat Virus: Its Extensive Validation and Novel Strategy |
| title_full | A Productive Expression Platform Derived from Host-Restricted Eilat Virus: Its Extensive Validation and Novel Strategy |
| title_fullStr | A Productive Expression Platform Derived from Host-Restricted Eilat Virus: Its Extensive Validation and Novel Strategy |
| title_full_unstemmed | A Productive Expression Platform Derived from Host-Restricted Eilat Virus: Its Extensive Validation and Novel Strategy |
| title_short | A Productive Expression Platform Derived from Host-Restricted Eilat Virus: Its Extensive Validation and Novel Strategy |
| title_sort | productive expression platform derived from host restricted eilat virus its extensive validation and novel strategy |
| topic | Eilat virus expression platform insect-specific diagnostic tool vaccine candidate |
| url | https://www.mdpi.com/1999-4915/13/4/660 |
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