In an effort to determine why the H5N1 virus is more virulent for ferrets than seasonal influenza A isolates, Cameron et al. (2008) analyzed the expression of host innate immune response genes during the course of lethal infection. The authors found that many interferon response genes, including IFI44, ISG15 (G1P2), MX2, OAS1, OAS2, STAT1, TAP1, and UBE1L, were significantly upregulated ferrets infected with the H5N1 virus, in comparison to an H3N2 isolate. CXCL10, a chemoattractant of activated Th1 lymphocytes and natural killer cells, was also upregulated to a much greater extent in an H5N1 infection than with the H3N2 virus. CXCL10 and its receptor CXCR3 are thought to play a role in the temporal development of innate and adaptive immunity in concert with type I and II interferons (Neville et al., 1997). In support of that hypothesis, Cameron et al. (2008) found that treatment of H5N1-infected ferrets with AMG487, a CXCR3 antagonist, markedly reduced the severity of symptoms and delayed death, compared to untreated animals.