Details

Autor(en) / Beteiligte

• Shirey, Kari Ann
• Nhu, Quan M.
• Yim, Kevin C.
• Roberts, Zachary J.
• Teijaro, John R.
• Farber, Donna L.
• Blanco, Jorge C.
• Vogel, Stefanie N.

Titel

The anti-tumor agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), induces IFN-β-mediated antiviral activity in vitro and in vivo

Ist Teil von

• Journal of leukocyte biology, 2011-03, Vol.89 (3), p.351-357

Ort / Verlag

United States: Society for Leukocyte Biology

Erscheinungsjahr

2011

Quelle

Wiley Blackwell Single Titles

Beschreibungen/Notizen

• The experimental anti‐tumor compound, DMXAA, shown previously to be a potent IFN‐β‐inducer in vitro, exhibits antiviral activity in vitro and in vivo. The 2009 outbreak of pandemic H1N1 influenza, increased drug resistance, and the significant delay in obtaining adequate numbers of vaccine doses have heightened awareness of the need to develop new antiviral drugs that can be used prophylactically or therapeutically. Previously, we showed that the experimental anti‐tumor drug DMXAA potently induced IFN‐β but relatively low TNF‐α expression in vitro. This study confirms these findings in vivo and demonstrates further that DMXAA induces potent antiviral activity in vitro and in vivo. In vitro, DMXAA protected RAW 264.7 macrophage‐like cells from VSV‐induced cytotoxicity and moreover, inhibited replication of influenza, including the Tamiflu®‐resistant H1N1 influenza A/Br strain, in MDCK cells. In vivo, DMXAA protected WT C57BL/6J but not IFN‐β−/− mice from lethality induced by the mouse‐adapted H1N1 PR8 influenza strain when administered before or after infection. Protection was accompanied by mitigation of weight loss, increased IFN‐β mRNA and protein levels in the lung, and significant inhibition of viral replication in vivo early after DMXAA treatment. Collectively, this study provides data to support the use of DMXAA as a novel antiviral agent.