Evaluation of two inoculation routes of an adenovirus-mediated viral protein inhibitor in a Crimean-Congo hemorrhagic fever mouse model

• DOI: 10.1016/j.virusres.2024.199398
• Publication Date: 2024-05-20T22:51:10Z
• Authors: Florine E.M. Scholte; Jessica R. Spengler; Stephen R. Welch; Jessica R. Harmon; JoAnn D. Coleman-...; Katherine A. Davies; Scott D. Pegan; Joel M. Montgomery; Christina F. Spir...; Éric Bergeron
• Keywords: Adenovirus infection; Viral protein

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne nairovirus with wide geographic spread that can cause severe and lethal disease. No specific medical countermeasures are approved to combat this illness. The CCHFV L protein contains an ovarian tumor (OTU) domain cysteine protease thought modulate cellular immune responses by removing ubiquitin ISG15 post-translational modifications from host viral proteins. Viral deubiquitinases like OTU attractive drug targets, as blocking their activity may enhance infection, potentially inhibit replication itself. We previously demonstrated the engineered variant CC4 potent inhibitor of in vitro. A major challenge therapeutic use small inhibitors such requirement for intracellular delivery, e.g., vectors. In study, we examined feasibility vivo delivery replication-deficient recombinant adenovirus (Ad-CC4) mouse model. Since liver primary target aimed optimize organ comparing intravenous (tail vein) intraperitoneal injection Ad-CC4. While tail vein traditional route our hands resulted higher more widespread levels genome tissues, including, intended, liver. However, despite promising vitro results, neither treatment protection infection.