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The B18R protein, which is encoded by the B18R open reading frame in the Western Reserve (WR) strain of vaccinia virus, is a type I interferon (IFN)-binding protein that is known to inhibit IFN antiviral response (Colamonici et al.). B18R protein has been shown to exhibit neutralizing activity to type I interferon family members (Meyers et al.) and to protect cells from the antiviral effects of interferon (Vancová et al.). It was recently shown that HIV-1–dependent induction of type I IFN activity and BAFF protein levels was abrogated by the soluble B18R protein, with no effect observed on the cell viability (Gomez et al.). B18R protein has been reported to aid in cellular reprogramming using RNA-mediated gene delivery (Warren et al.; Yoshioka N et al.).