Diversity, Replication, Pathogenicity and Cell Biology of Crimean Congo Hemorrhagic Fever Virus
Abstract
This research project was a result of a collaboration between three research groups aimed at elucidating basic replication processes of CCHFV with the expected outcome of providing basic research reagents and establishing the foundation of knowledge necessary for discovery of vaccines and antiviral therapeutics for Crimean Congo hemorrhagic fever. Our major findings during the total period of support were the following: We have cloned and expressed all proteins of CCHFV. We found that the protease activity associated with the N-terminal of the L protein is responsible for overcoming innate immune responses mediated by ubiquitin and by the ubiquitin-like molecule ISG15. We have characterized in detail the processing of the G protein and the expression of the NSm protein of CCHFV, and developed constructs with fusogenic activity based on expression of the G ORF. We have successfully passaged CCHFV 18 times in SCID mice and conducted preliminary studies in macaques. Our results have provided novel insights on the molecular biology of this understudied highly pathogenic human virus and opened new avenues for the discovery of CCHFV antivirals.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2008
- Accession Number
- ADA502011
Entities
People
- Adolfo García-Sastre
Organizations
- Icahn School of Medicine at Mount Sinai