Tetracistronic minigenomes elucidate a functional promoter for Ghana virus and unveils Cedar virus replicase promiscuity for all henipaviruses
- Authors
- Type
- Published Article
- Journal
- Journal of Virology
- Publisher
- American Society for Microbiology
- Publication Date
- Sep 30, 2024
- Volume
- 98
- Issue
- 10
- Identifiers
- DOI: 10.1128/jvi.00806-24
- Source
- ASM Journals
- Keywords
- License
- Green
Abstract
Henipaviruses are recognized as significant global health threats due to their high mortality rates and lack of effective vaccines or therapeutics. Due to the requirement for high biocontainment facilities, the scope of research which may be conducted on henipaviruses is limited. To address this challenge, we developed innovative tetracistronic, transcription, and replication-competent minigenomes. We demonstrate that these systems replicate key aspects of the viral life cycle, such as budding, fusion, and receptor binding, and are safe for use in lower biocontainment settings. Importantly, the application of this system to the Ghana virus revealed that its known sequence is incomplete; however, substituting the missing sequences with those from other henipaviruses allowed us to overcome this challenge. We demonstrate that the Ghana virus replicative machinery is functional and can identify two orally efficacious antivirals effective against it. Our research offers a versatile system for life-cycle modeling of highly pathogenic henipaviruses at low biocontainment.
