A Kinome RNAi Screen Identified AMPK as Promoting Poxvirus Entry through the Control of Actin Dynamics

PLoS Pathogens

Craig B. Thompson¹  Carolyn B. Coyne²  Sara Cherry³  Theresa S. Moser³  Russell G. Jones⁴ 

[1] Department of Cancer Biology, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America;Department of Microbiology and Molecular Genetics, The University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America;Department of Microbiology, Penn Genome Frontiers Institute, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America;Goodman Cancer Center and Department of Physiology, McGill University, Montreal, Quebec, Canada

关键词: Drosophila melanogaster;    Actins;    Vaccinia virus;    RNA interference;    Cytoskeleton;    Cell membranes;    Immunofluorescence;    Tyrosine kinases;   

DOI  :  10.1371/journal.ppat.1000954

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Poxviruses include medically important human pathogens, yet little is known about the specific cellular factors essential for their replication. To identify genes essential for poxvirus infection, we used high-throughput RNA interference to screen the Drosophila kinome for factors required for vaccinia infection. We identified seven genes including the three subunits of AMPK as promoting vaccinia infection. AMPK not only facilitated infection in insect cells, but also in mammalian cells. Moreover, we found that AMPK is required for macropinocytosis, a major endocytic entry pathway for vaccinia. Furthermore, we show that AMPK contributes to other virus-independent actin-dependent processes including lamellipodia formation and wound healing, independent of the known AMPK activators LKB1 and CaMKK. Therefore, AMPK plays a highly conserved role in poxvirus infection and actin dynamics independent of its role as an energy regulator.

【 授权许可】

CC BY