Class
Article
College
College of Agriculture and Applied Sciences
Department
Animal, Dairy, and Veterinary Sciences Department
Faculty Mentor
Justin Julander
Presentation Type
Poster Presentation
Abstract
Yellow fever virus (YFV) is a mosquito-borne virus with a considerable disease burden in South America and Africa and no approved antivirals. BDAA is an experimental antiviral for YFV which inhibits the viral protein NS4B and is effective against YFV in cell culture and a hamster model. Along with directly inhibiting virus replication, treating YFV-infected cells with BDAA increases the detection and response to foreign RNA by the host cell by releasing YFV replication intermediates into the cytoplasm. While this has been shown in cell culture, it is important to understand if this immune effect is relevant to BDAA’s efficacy in an animal model. We demonstrated the effect of treating YFV with BDAA on inflammatory cytokines and apoptosis in liver tissue using IFNAR-/- mouse and Syrian golden hamster models. We also reaffirm BDAA’s efficacy against YFV in the hamster model. When the hamsters were treated with 200 mg/kg/d BDAA, initiated 4 hours pre-infection or 2 days post-infection (dpi) and continuing for 7 days, survival, levels of virus in the serum, weight change, and measures of liver damage (ALT and histopathology) were improved. BDAA treatment initiated 4 hours pre-infection and 2 dpi resulted in 100% survival compared to complete mortality in placebo-treated hamsters (p < 0.0001 for both). Histopathology shows decreased necrosis in liver tissue when treatment is initiated at 2 dpi compared to placebo-treated animals and no visible liver necrosis in prophylactic treatment. These results further demonstrate BDAA’s efficacy against YFV in animal models and support the potential of NS4B inhibitors like BDAA as treatments for YFV.
Location
Logan, UT
Start Date
4-11-2023 10:30 AM
End Date
4-11-2023 11:30 AM
Treating Yellow Fever Virus With the Antiviral BDAA and Effects on the Immune Response in an Animal Model
Logan, UT
Yellow fever virus (YFV) is a mosquito-borne virus with a considerable disease burden in South America and Africa and no approved antivirals. BDAA is an experimental antiviral for YFV which inhibits the viral protein NS4B and is effective against YFV in cell culture and a hamster model. Along with directly inhibiting virus replication, treating YFV-infected cells with BDAA increases the detection and response to foreign RNA by the host cell by releasing YFV replication intermediates into the cytoplasm. While this has been shown in cell culture, it is important to understand if this immune effect is relevant to BDAA’s efficacy in an animal model. We demonstrated the effect of treating YFV with BDAA on inflammatory cytokines and apoptosis in liver tissue using IFNAR-/- mouse and Syrian golden hamster models. We also reaffirm BDAA’s efficacy against YFV in the hamster model. When the hamsters were treated with 200 mg/kg/d BDAA, initiated 4 hours pre-infection or 2 days post-infection (dpi) and continuing for 7 days, survival, levels of virus in the serum, weight change, and measures of liver damage (ALT and histopathology) were improved. BDAA treatment initiated 4 hours pre-infection and 2 dpi resulted in 100% survival compared to complete mortality in placebo-treated hamsters (p < 0.0001 for both). Histopathology shows decreased necrosis in liver tissue when treatment is initiated at 2 dpi compared to placebo-treated animals and no visible liver necrosis in prophylactic treatment. These results further demonstrate BDAA’s efficacy against YFV in animal models and support the potential of NS4B inhibitors like BDAA as treatments for YFV.