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- Title
Developing Broad-Spectrum Antivirals Using Porcine and Rhesus Macaque Models.
- Authors
Qiu, Xueer; Taft, Justin; Bogunovic, Dusan
- Abstract
ISG15-deficient humans exhibit permanent, low-level expression of antiviral effectors that safely protect them from various viruses. Because the murine ISG15 axis functions differently, we identified animal models that recapitulate the human condition for the development of ISG15-targeting broad-spectrum antivirals. Canine, porcine, and rhesus macaque ISG15, such as human ISG15, stabilize USP18, a potent inhibitor of type I interferon (IFN)-I. Type I Interferon-primed ISG15-knockout porcine and rhesus cells demonstrate enhanced ISG expression and protection against vesicular stomatitis Indiana virus infection compared with wild type. Collectively, we unveil the interspecies diversity of the ability of ISG15/USP18 axis to control IFN-I signaling and reveal the therapeutic potential of ISG15-deficient porcine and rhesus models.
- Subjects
INDIANA; RHESUS monkeys; TYPE I interferons; ANTIVIRAL agents; VESICULAR stomatitis; VIRUS diseases; PROTEIN metabolism; ANIMAL experimentation; CELL culture; COMPARATIVE studies; CYTOKINES; ESTERASES; BIOLOGICAL evolution; GENES; IMMUNITY; RESEARCH methodology; MEDICAL cooperation; GENETIC mutation; PRIMATES; RESEARCH; SWINE; EVALUATION research; PHARMACODYNAMICS
- Publication
Journal of Infectious Diseases, 2020, Vol 221, Issue 6, p890
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiz549