While the data show that NF-kB is required for viral SOCS-3 induction, the factor appears not to be sufficient, since prototype inducers of NF-kB, such as IL-1b or TNF-a would not induce SOCS-3. Thus there seems to be the need of additional virus or RNA-induced transcription factors. The most likely candidate would be the constitutively expressed interferon regulatory factor 3 (IRF-3), that is known to be simultaneously activated with NF-kB upon virus infection directly via the RIG-I RNA sensing pathway without the need of type I IFN. Furthermore IRF-3 is a factor suppressed by the NS1 protein.