Regulatory roles of c-jun in H5N1 influenza virus replication and host inflammation

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Authors
  1. Wang, M.
  2. Xie, J.
  3. Hu, Y.
  4. Li, D.
  5. Cui, J
  6. Zhang, S.
  7. Xue, J.
  8. Zhang, G.
  9. Khachigian, L.M.
  10. Wong, J.
  11. Sun L.
  12. Wang, M.
Corporate Authors
Defence Research and Development Canada, Suffield Research Centre, Ralston AB (CAN)
Abstract
The cytokine stormwhich is a great burden on humanity in highly pathogenic influenza virus infections requires 23 activation of multiple signaling pathways. These pathways, such asMAPK and JNK, are important for viral repli- 24 cation and host inflammatory response. Here we examined the roles of JNK downstream molecule c-jun in host 25 inflammatory responses and H5N1 virus replication using a c-jun targeted DNAzyme (Dz13). Transfection of 26 Dz13 significantly reduced H5N1 influenza virus replication in human lung epithelial cells. Concomitantly, 27 there was a decreased expression of pro-inflammatory cytokines (tumor necrosis factor (TNF)-¦Á, interferon 28 (IFN)-¦Â and interleukin (IL)-6) in c-jun suppressed cells, while the expression of anti-inflammatory cytokines, 29 such as IL-10, was increased. In vivo, compared with control groups, suppression of c-jun improved the survival 30 rate of mice infected with H5N1 virus (55.5% in Dz13 treated mice versus ¡Ü11% of control mice) and decreased 31 the CD8+ T cell proliferation. Simultaneously, the pulmonary inflammatory response and viral burden also de- 32 creased in the Dz13 treated group. Thus, our data demonstrated a critical role for c-jun in the establishment of 33 H5N1 infection and subsequent inflammatory reactions, which suggest that c-junmay be a potential therapeutic 34 target for viral pneumonia.
Keywords
inflammation;c-jun;DNAzyme
Report Number
DRDC-RDDC-2016-P012 — External Literature
Date of publication
18 Apr 2016
Number of Pages
10
DSTKIM No
CA041929
CANDIS No
803088
Format(s):
Electronic Document(PDF)

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