期刊
JOURNAL OF INFECTIOUS DISEASES
卷 221, 期 6, 页码 890-894出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiz549
关键词
broad-spectrum antiviral; ISG15 deficiency; USP18
资金
- National Institute of Allergy and Infectious Disease Grants [R01AI127372, R21AI134366, R21AI129827]
- March of Dimes
- Ruth L. Kirschstein Predoctoral Individual National Research Service Award [FAI138363A]
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.
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