Tetracistronic Minigenomes Elucidate a Functional Promoter for Ghana Virus and Unveils Cedar Virus Replicase Promiscuity for all Henipaviruses.
| العنوان: | Tetracistronic Minigenomes Elucidate a Functional Promoter for Ghana Virus and Unveils Cedar Virus Replicase Promiscuity for all Henipaviruses. |
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| المؤلفون: | Haas GD; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY., Schmitz KS; Department of Viroscience, Erasmus MC, 3015 GD Rotterdam, The Netherlands., Azarm KD; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY., Johnson KN; Department of Pathology, University of Texas Medical Branch, Galveston, TX., Klain WR; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY., Freiberg AN; Department of Pathology, University of Texas Medical Branch, Galveston, TX., Cox RM; Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA., Plemper RK; Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA., Lee B; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 16. Date of Electronic Publication: 2024 Apr 16. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Batborne henipaviruses, such as Nipah virus and Hendra virus, represent a major threat to global health due to their propensity for spillover, severe pathogenicity, and high mortality rate in human hosts. Coupled with the absence of approved vaccines or therapeutics, work with the prototypical species and uncharacterized, emergent species is restricted to high biocontainment facilities. There is a scarcity of such specialized spaces for research, and often the scope and capacity of research which can be conducted at BSL-4 is limited. Therefore, there is a pressing need for innovative life-cycle modeling systems to enable comprehensive research within lower biocontainment settings. This work showcases tetracistronic, transcription and replication competent minigenomes for Nipah virus, Hendra virus, Cedar virus, and Ghana virus, which encode viral proteins facilitating budding, fusion, and receptor binding. We validate the functionality of all encoded viral proteins and demonstrate a variety of applications to interrogate the viral life cycle. Notably, we found that the Cedar virus replicase exhibits remarkable promiscuity, efficiently rescuing minigenomes from all tested henipaviruses. We also apply this technology to GhV, an emergent species which has so far not been isolated in culture. We demonstrate that the reported sequence of GhV is incomplete, but that this missing sequence can be substituted with analogous sequences from other henipaviruses. Use of our GhV system establishes the functionality of the GhV replicase and identifies two antivirals which are highly efficacious against the GhV polymerase. |
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| معلومات مُعتمدة: | T32 AI007647 United States AI NIAID NIH HHS; R01 AI071002 United States AI NIAID NIH HHS; T32 AI060549 United States AI NIAID NIH HHS; U19 AI171403 United States AI NIAID NIH HHS; R21 AI149033 United States AI NIAID NIH HHS |
| تواريخ الأحداث: | Date Created: 20240425 Latest Revision: 20240502 |
| رمز التحديث: | 20240502 |
| مُعرف محوري في PubMed: | PMC11042316 |
| DOI: | 10.1101/2024.04.16.589704 |
| PMID: | 38659760 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2024.04.16.589704 |
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