Researchers at the Novartis Institute for Tropical Diseases and the Genome Institute of Singapore have identified new host genes associated with dengue virus infection, which may open new avenues to developing a drug to treat the disease.
Dengue is the most prevalent mosquito-born viral disease affecting humans. Dengue-related disease results in an estimated 50-100 million cases of dengue fever and 250,000 to 500,000 cases of dengue hemorrhagic fever/dengue shock syndrome each year. Yet there is, at present, no drug treatment at all for the disease nor are there any validated host targets for therapeutic intervention.
Using microarray technology to monitor the response of virtually every human gene, Dr Subhash Vasudevan and Dr. Martin Hibberd’s team aimed to identify the ways in which humans interact with dengue virus during infection in order to discover new treatment targets that could be exploited to control viral replication.
From the activated genes, the researchers identified three pathways common to in vitro and in vivo infection; the NF-kappaB initiated immune pathway, the type I interferon pathway, and the ubiquitin proteasome pathway. They next found that inhibiting the ubiquitin proteasome pathway, or activating the type I interferon pathway, resulted in significant inhibition of viral replication whereas inhibiting the NF-kappaB initiated immune pathway had no effect on viral replication. These results suggest that drugs that target the host pathways may prove effective against dengue.
CITATION: Fink J, Gu F, Ling L, Tolfvenstam T, Olfat F, et al. (2007) Host Gene Expression Profiling of Dengue Virus Infection in Cell Lines and Patients. PLoS Negl Trop Dis 1(2): e86. doi:10.1371/journal.pntd.0000086
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