ISG15 KO mice show altered host response to viral infection
Reference Number TO 08-00021
Challenge
Type I interferons (IFNs) play an essential role in the host response to viral infection through the induction of numerous IFN-stimulated genes (ISGs), including important antiviral molecules such as PKR, RNase L, Mx, and iNOS. Yet, additional antiviral ISGs likely exist. IFN-stimulated gene 15 (ISG15) is a ubiquitin homolog that is rapidly up-regulated after viral infection, and it conjugates to a wide array of host proteins. Although it has been hypothesized that ISG15 functions as an antiviral molecule, the initial evaluation of ISG15-deficient mice revealed no defects in their responses to vesicular stomatitis virus or lymphocytic choriomeningitis virus, leaving open the important question of whether ISG15 is an antiviral molecule in vivo.
Technology
New data demonstrate that ISG15 is critical for the host response to viral infection. ISG15 (-/-) mice are more susceptible to influenza A/WSN/33 and influenza B/Lee/40 virus infections. ISG15 (-/-) mice also exhibited increased susceptibility to both herpes simplex virus type 1 and murine gammaherpesvirus 68 infection and to Sindbis virus infection. The increased susceptibility of ISG15 (-/-) mice to Sindbis virus infection was rescued by expressing wild-type ISG15, but not a mutant form of ISG15 that cannot form conjugates, from the Sindbis virus genome. The demonstration of ISG15 as a novel antiviral molecule with activity against both RNA and DNA viruses provides a target for the development of therapies against important human pathogens.
Further studies demonstrated a role for ISG15 not only in cellular defense from infections but also a possible role for ISG15 in carcinogenesis and cancer therapy.
Commercial Opportunity
Breeding pairs are available under a Tangible Property License Agreement.
Furter Reading
Lenschow et al.; IFN-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and Sindbis viruses. PNAS January 23, 2007; vol. 104, no. 4; 1371-1376
Pitha-Rowe et al.; Viral defense, carcinogenesis and ISG15: Novel roles for an old ISG. Cytokine & Growth Factor Reviews 18 (2007) 409-417
