Antiviral activity of adenoviral vector expressing human interferon lambda-4 against influenza virus

Interferon lambda (IFN lambda), classified as a type III IFN, is a representative cytokine that plays an important role in innate immunity along with type I IFN. IFN lambda can elicit antiviral states by inducing peculiar sets of IFN-stimulated genes (ISGs). In this study, an adenoviral vector expression system with a tetracycline operator system was used to express human IFN lambda 4 in cells and mice. The formation of recombinant adenovirus (rAd-huIFN lambda 4) was confirmed using immunohistochemistry assays and transmission electron microscopy. Its purity was verified by quantifying host cell DNA and host cell proteins, as well as by confirming the absence of the replication-competent adenovirus. The transduction of rAd-huIFN lambda 4 induced ISGs and inhibited four subtypes of the influenza virus in both mouse-derived (LA-4) and human-derived cells (A549). The antiviral state was confirmed in BALB/c mice following intranasal inoculation with 109 PFU of rAd-huIFN lambda 4, which led to the inhibition of four subtypes of the influenza virus in mouse lungs, with reduced inflammatory lesions. These results imply that human IFN lambda 4 could induce antiviral status by modulating ISG expression in mice.