A kinome RNAi screen identified AMPK as promoting poxvirus entry through the control of actin dynamics.
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.
Moser
Theresa S
TS
Department of Microbiology, Penn Genome Frontiers Institute, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
Jones
Russell G
RG
Thompson
Craig B
CB
Coyne
Carolyn B
CB
Cherry
Sara
S
D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D000199:Actins / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D002465:Cell Movement; D002478:Cells, Cultured; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D049750:Genome, Insect; D015151:Immunoblotting; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D010873:Pinocytosis; D011494:Protein Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011554:Pseudopodia; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014615:Vaccinia / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D014616:Vaccinia virus / Q000502:physiology*; D053586:Virus Internalization; D014779:Virus Replication; D014945:Wound Healing
D000199:Actins; D012333:RNA, Messenger; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases