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A kinome RNAi screen identified AMPK as promoting poxvirus entry through the control of actin dynamics

Theresa S Moser1, Russell G Jones, Craig B Thompson

  • 1Department of Microbiology, Penn Genome Frontiers Institute, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.

Plos Pathogens
|June 30, 2010
PubMed

Insights

AMP-activated protein kinase (AMPK) promotes vaccinia virus infection in both insect and mammalian cells. This conserved kinase is essential for viral entry via macropinocytosis and other actin-driven cellular processes.

Area of Science:

  • Virology
  • Cell Biology
  • Biochemistry

Background:

  • Poxviruses are significant human pathogens with poorly understood replication mechanisms.
  • Identifying cellular factors essential for poxvirus replication is crucial for understanding infection.

Purpose of the Study:

  • To identify host cell genes critical for vaccinia virus infection using a high-throughput screen.
  • To investigate the role of AMP-activated protein kinase (AMPK) in poxvirus replication and cellular processes.

Main Methods:

  • Conducted a high-throughput RNA interference screen in Drosophila to identify host factors for vaccinia infection.
  • Validated identified genes, including AMPK subunits, in both insect and mammalian cells.
  • Assessed AMPK's role in macropinocytosis, lamellipodia formation, and wound healing.

Main Results:

  • Identified seven genes, including the three subunits of AMPK, that promote vaccinia infection.
  • Demonstrated that AMPK facilitates vaccinia infection in both insect and mammalian cells.
  • Showed AMPK is essential for macropinocytosis, a key viral entry pathway.
  • Revealed AMPK's involvement in virus-independent, actin-dependent processes like lamellipodia formation and wound healing, independent of LKB1 and CaMKK.

Conclusions:

  • AMP-activated protein kinase (AMPK) plays a conserved role in poxvirus infection.
  • AMPK is crucial for vaccinia virus entry through macropinocytosis.
  • AMPK regulates actin dynamics in conserved, virus-independent cellular processes, distinct from its energy metabolism role.

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