Dynamic changes in host gene expression associated with H5N8 avian influenza virus infection in mice

Su Jin Park, Mukesh Kumar, Hyeok Il Kwon, Rak Kyun Seong, Kyudong Han, Jae Min Song, Chul Joong Kim, Young Ki Choi, Ok Shin

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Abstract

Emerging outbreaks of newly found, highly pathogenic avian influenza (HPAI) A(H5N8) viruses have been reported globally. Previous studies have indicated that H5N8 pathogenicity in mice is relatively moderate compared with H5N1 pathogenicity. However, detailed mechanisms underlying avian influenza pathogenicity are still undetermined. We used a high-throughput RNA-seq method to analyse host and pathogen transcriptomes in the lungs of mice infected with A/MD/Korea/W452/2014 (H5N8) and A/EM/Korea/W149/2006 (H5N1) viruses. Sequenced numbers of viral transcripts and expression levels of host immune-related genes at 1 day post infection (dpi) were higher in H5N8-infected than H5N1-infected mice. Dual sequencing of viral transcripts revealed that in contrast to the observations at 1 dpi, higher number of H5N1 genes than H5N8 genes was sequenced at 3 and 7 dpi, which is consistent with higher viral titres and virulence observed in infected lungs in vivo. Ingenuity pathway analysis revealed a more significant upregulation of death receptor signalling, driven by H5N1 than with H5N8 infection at 3 and 7 dpi. Early induction of immune response-related genes may elicit protection in H5N8-infected mice, which correlates with moderate pathogenicity in vivo. Collectively, our data provide new insight into the underlying mechanisms of the differential pathogenicity of avian influenza viruses.

Original languageEnglish
Article number16512
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 2015 Nov 18

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Park, S. J., Kumar, M., Kwon, H. I., Seong, R. K., Han, K., Song, J. M., Kim, C. J., Choi, Y. K., & Shin, O. (2015). Dynamic changes in host gene expression associated with H5N8 avian influenza virus infection in mice. Scientific Reports, 5, [16512]. https://doi.org/10.1038/srep16512