Diversity, Replication, Pathogenicity and Cell Biology of Crimean Congo Hemorrhagic Fever Virus
Abstract
This research project is 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 third year of support are the following: We have demonstrated that the isopeptidase 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, and that this activity is shared with the nsp2 of an unrelated virus family: the arteriviruses. This activity could be a target for antiviral development. We have characterized in more detail 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 provide novel insights on the molecular biology of this understudied highly pathogenic human virus.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2007
- Accession Number
- ADA475148
Entities
People
- Adolfo García-Sastre
Organizations
- Icahn School of Medicine at Mount Sinai