To circumvent the fast decay of cIFN-a, a replicationincompetent, recombinant adenovirus type 5 (rAd5) gene delivery platform was designed to drive constitutive expression of the cIFNa gene from transduced nasal epithelial target cells. This rAd5 cIFN-a virus, called DEF201, was first developed in mice and recently shown to be active against yellow fever virus (YFV) infection in hamsters [19, 20] . The intranasal (i.n.) inoculation used in the YFV study prevents the host immune system from recognizing the Ad5 vector, thereby bypassing any possible preexisting immunity [21] . In the present study, we evaluated the use of DEF201 administered i.n. for the prevention and treatment of PICV infection in hamsters.