Gene Expression Analysis of Host Innate Immune Responses during Lethal H5N1 Infection in Ferrets

摘要: How viral and host factors contribute to the severe pathogenicity of H5N1 subtype avian influenza virus infection in humans is poorly understood. We identified three clusters differentially expressed innate immune response genes lungs from (A/Vietnam/1203/04) virus-infected ferrets by oligonucleotide microarray analysis. Interferon were more strongly H5N1-infected ferret than infected with less pathogenic H3N2 subtype. In particular, robust CXCL10 gene expression led us test role signaling via CXCL10's cognate receptor, CXCR3, during infection. Treatment drug AMG487, a CXCR3 antagonist, resulted reduction symptom severity delayed mortality compared vehicle treatment. contend that unregulated interferon responses are at least partially responsible for provide evidence attenuating pathway improves clinical course ferrets.