Format

Send to:

Choose Destination
See comment in PubMed Commons below
Antiviral Res. 2008 Nov;80(2):124-34. doi: 10.1016/j.antiviral.2008.05.008. Epub 2008 Jun 13.

Modulation of influenza virus replication by alteration of sodium ion transport and protein kinase C activity.

Author information

  • 1Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.

Abstract

In recent years, increasing levels of resistance to the four FDA-approved anti-influenza virus drugs have been described and vaccine manufacturers have experienced demands that exceed their capacity. This situation underlines the urgent need for novel antivirals as well as innovations in vaccine production in preparation for the next influenza epidemic. Here we report the development of a cell-based high-throughput screen which we have used for the identification of compounds that modulate influenza virus growth either negatively or positively. We screened a library of compounds with known biological activity and identified distinct groups of inhibitors and enhancers that target sodium channels or protein kinase C (PKC). We confirmed these results in viral growth assays and find that treatment with a sodium channel opener or PKC inhibitor significantly reduces viral replication. In contrast, inhibition of sodium channels or activation of PKC leads to enhanced virus production in tissue culture. These diametrically opposing effects strongly support a role for PKC activity and the regulation of Na(+) currents in influenza virus replication and both may serve as targets for antiviral drugs. Furthermore, we raise the possibility that compounds that result in increased viral titers may be beneficial for boosting the production of tissue culture-grown influenza vaccines.

PMID:
18585796
[PubMed - indexed for MEDLINE]
PMCID:
PMC2614658
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk