Username


Password

Forgot Password?

Preview

Sign-in free and Explore the Exciting World of BiomedExperts:
  • Over 1.500.000 Profiles
  • More than 1.800 Organizations worldwide
  • State of the Art Network Visualizations
  • Manage your own Profile
  • Locate Experts in your Country/Region
  • Locate Experts in your 1. and 2. Level Network
  • Connect to Experts Worldwide

find experts for

Sign-in to see more
2007: Goodman Alan G; Smith Jennifer A; Balachandran Siddharth; Perwitasari Olivia; Proll Sean C; Thomas Matthew J; Korth Marcus J; Barber Glen N; Schiff Leslie A; Katze Michael G
The cellular protein P58IPK regulates influenza virus mRNA translation and replication through a PKR-mediated mechanism.
Journal of virology 2007;81(5):2221-30.
We previously hypothesized that efficient translation of influenza virus mRNA requires the recruitment of P58(IPK), the cellular inhibitor of PKR, an interferon-induced kinase that targets the eukaryotic translation initiation factor eIF2alpha. P58(IPK) also inhibits PERK, an eIF2alpha kinase that is localized in the endoplasmic reticulum (ER) and induced during ER stress. The ability of P58(IPK) to interact with and inhibit multiple eIF2alpha kinases suggests it is a critical regulator of both cellular and viral mRNA translation. In this study, we sought to definitively define the role of P58(IPK) during viral infection of mammalian cells. Using mouse embryo fibroblasts from P58(IPK-/-) mice, we demonstrated that the absence of P58(IPK) led to an increase in eIF2alpha phosphorylation and decreased influenza virus mRNA translation. The absence of P58(IPK) also resulted in decreased vesicular stomatitis virus replication but enhanced reovirus yields. In cells lacking the P58(IPK) target, PKR, the trends were reversed-eIF2alpha phosphorylation was decreased, and influenza virus mRNA translation was increased. Although P58(IPK) also inhibits PERK, the presence or absence of this kinase had little effect on influenza virus mRNA translation, despite reduced levels of eIF2alpha phosphorylation in cells lacking PERK. Finally, we showed that influenza virus protein synthesis and viral mRNA levels decrease in cells that express a constitutively active, nonphosphorylatable eIF2alpha. Taken together, our results support a model in which P58(IPK) regulates influenza virus mRNA translation and infection through a PKR-mediated mechanism which is independent of PERK.

Post to CiteULike

Sign in free and see...

Visualized networks:
See your personal network in
sophisticated graphical views
GeoTargeted Searches:
Locate experts around the world
and connect with global collaborators
Research Profiles:
See the visualized research activity
of experts around the globe
Sign-in to see more