The avian and mammalian toll-like receptors 7 and 8 are usually present in the endosomal compartments, where they are responsible for detecting the single-stranded RNAs of Sibutramine HCl viruses engulfed via endocytosis. How TLRs 7 and 8 discriminate between self and non-self RNAs is not clear. However, published data indicate that nucleotide composition is crucial. Diversity in viral genome sequences results in differences in nucleotide composition that may affect the stimulatory activity that viral RNAs exert on host TLRs. Genome sequence diversity may thus provide a way for single-stranded RNA viruses to evade host innate immunity. Very few attempts have been made to examine these types of virus-host interactions computationally. It is well known that the NS1 protein is an immunosuppressor. It inhibits innate immunity by preventing type I IFN release, and it inhibits adaptive immunity by attenuating human DC maturation and reducing the capacity of DCs to induce a T-cell Raddeanin-A response. However, the effects of NS1 occur after successful infection, viral RNA transcription and viral protein production. Before viral RNA transcription and protein production can take place, single-stranded RNA viruses must first conquer another innate immune mechanism: the toll-like receptors 7 and 8 of the host cells. To evaluate the diversity of interactions between viral genomic RNAs and host TLR 7/8, we devise a novel viral genomic trait called TSTC and derive two scores called TSSs. A comparison of the TSS distributions from each genomic RNA and from the whole genomes of human, avian and mammalian IAVs revealed that there are large differences between human and avian IAV genomes, as indicated by Score S and Score N, except for segment 3. Moreover, we found that a low Score S is associated with high pathogenicity/pandemic potential of IAVs. The algorithm proposed in this study was based on the identified TLR stimulatory activities of naked synthetic oligos. However, Influenza viruses are enveloped and negative-sensed RNA viruses and the virus genomes are composed of ribonucleoproteins instead of naked RNAs.