Kinome siRNA screen identifies novel cell-type specific dengue host target genes.

Kinome siRNA screen identifies novel cell-type specific dengue host target genes.
Antiviral Res. 2014 Jul 18;
Authors: Kwon YJ, Heo J, Wong HE, Cruz DJ, Velumani S, da Silva CT, Mosimann AL, Duarte Dos Santos CN, Freitas-Junior LH, Fink K
Abstract
Dengue is a global emerging infectious disease, with no specific treatment available. To identify novel human host cell targets important for dengue virus infection and replication, an image-based high-throughput siRNA assay screening of a human kinome siRNA library was conducted using human hepatocyte cell line Huh7 infected with a recent dengue serotype 2 virus isolate BR DEN2 01-01. In the primary siRNA screening of 779 kinase-related genes, knockdown of 22 genes showed a reduction in DENV-2 infection. Conversely, knockdown of 8 genes enhanced viral infection. To assess host cell specificity, the confirmed hits were tested in the DENV-infected monocytic cell line U937. While the expression of EIF2AK3, ETNK2 and SMAD7 was regulated in both cell lines after infection, most kinases were hepatocyte-specific. Monocytic cells represent initial targets of infection and an anti-viral treatment targeting these cells is probably most effective to reduce initial viral load. In turn, infection of the liver could contribute to pathogenesis, and the novel hepatocyte-specific human targets identified here could be important for dengue infection and pathogenesis.
PMID: 25046486 [PubMed - as supp...

Source: Antiviral Research - July 18, 2014 Category: Virology Authors: Kwon YJ, Heo J, Wong HE, Cruz DJ, Velumani S, da Silva CT, Mosimann AL, Duarte Dos Santos CN, Freitas-Junior LH, Fink K Tags: Antiviral Res Source Type: research